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Rediscovering Phage Therapy

By Emily Wilson, Philippe Vezina, and Mohammad Jafar Sami

Cases of antibiotic resistance have become a prominent concern for our healthcare system. Antibiotic resistance is a result of bacteria that have evolved to overcome antibiotic treatment. For instance, mutated bacteria may begin producing enzymes that give them resistance to antibiotics; this offers a selective advantage that allows the mutated strain to proliferate despite treatment. As a result of this public health concern, medical practitioners and researchers are on the search for alternative antimicrobial agents to complement the role of antibiotics. It is here that phage therapy may find its place in future clinical practice one century after its initial discovery.

What is Phage Therapy?

Phage therapy uses phages, also known as bacteriophages, to target and counteract infections. Phages are a form of virus which infect bacteria. Their structure consists of genetic material surrounded by a protein capsid which makes up the “head” of the bacteriophage. This structure is complemented by the phage tail which is used to target and secure the virus to bacterial hosts (Figure 1).

Figure 1: Basic phage structure. Source: Emily Wilson.

Phages were originally discovered by Frederick Twort and Felix d’Hérelle in the early 1900s. Shortly after their discovery, d’Hérelle managed to effectively apply phages as a treatment for dysentery infections, which at the time had no successful cure. While his success led to widespread enthusiasm for the potential of phage therapy, this treatment was quickly eclipsed in the western world with the introduction of antibiotics. However, it can be noted that the use of phage therapy has prevailed in various regions of the world, especially in the former Soviet Republic of Georgia where phages are standard in care.

How Does it All Work?

One of the biggest advantages of phage therapy is that phages are designed to be highly specific as a result of their ability to recognize bacterial cell surface receptors.  When a phage comes in contact with its target bacteria, there are a number of mechanisms by which the virion can impart its antimicrobial effects.  Phages can be harnessed for their potential to lyse bacteria through their lytic cycle and bactericidal enzymes as well as for their ability to increase the antibiotic sensitivity of target bacteria.

In the lytic cycle, phages replicate inside their target bacteria, making dozens of copies which will eventually destroy the bacterial cell so that these replicates may further disseminate into the environment (Figure 2).

Figure 2: The lytic cycle starts when the host bacterium (1) is targeted by the phage and injected with viral DNA (2). This phage DNA is then used to create phage proteins (3) which are assembled into complete phages (4). The cell then breaks apart releasing the newly generated phages into the environment (5). Source: Emily Wilson.

Phages may also be harnessed for their ability to produce enzymes that target bacteria. Considerable research in this area has focused on endolysins which are the peptidoglycan hydrolases involved in cell lysis during the lytic phage cycle. This means these enzymes are capable of disrupting the bacterial cell wall which leads to the death of the bacteria.

Instead of replicating within the bacteria leading to cell death, the phage may also incorporate its own genetic material into the genome of the bacteria. Through this mechanism, known as transduction, phages are capable of introducing novel characteristics to their bacterial host. This can be applied in the clinical setting as phages are able to reintroduce drug sensitivity to antibiotic resistant bacteria by introducing drug sensitive genes as shown in Figure 3.

Figure 3: Phages can introduce drug-sensitive genes into drug resistant host bacteria through transduction. In this process the recipient bacteria (1) is targeted by the phage carrying DNA with genes for drug sensitivity (2). When the DNA is injected (3) the bacteria will incorporate the viral DNA into its own genome (4), allowing for the expression of drug-sensitive genes. Source: Emily Wilson.

Where does Phage Therapy “Fit in”?

Antibiotics have taken the medical world by storm since their discovery in the early 1900s. These agents are highly effective at destroying bacteria in a broad range, non-specific manner making them a great tool to counteract infections. Antibiotics are nonspecific and therefore will attack both pathogenic and commensal bacteria which can lead to an imbalance and lack of regulation in the human microbiota. The human microbiota refers to the collection of commensal, or healthy bacteria that normally colonize the body. The microbiota serves a key role in the immune system’s first line of defense. Healthy bacteria inhibit the ability of pathogenic species to initiate colonization which is why the dysregulation of this system as a result of antibiotics can be problematic. Furthermore, overuse of antibiotics in healthcare has led to the development of antibiotic resistant bacteria.

Bacteria have three main mechanisms of antibiotic resistance. The bacterium may restrict exposure of the antibiotic to its target. For example, if the antibiotic’s target is inside the bacterial cell, the bacterium will stop expressing the transport system used to bring the antibiotic inside the cell. The antibiotic will be unable to reach its target and thus unable to affect the pathogen. The bacterium may also destroy or inactivate the antibiotic before it can reach its target rendering the treatment ineffective. Lastly, the bacterium may modify the antibiotic target so that the antibiotic is no longer able to bind and induce an effect. It has been predicted that by 2050, antimicrobial resistant infections will become the cause of more deaths than cancer.

This phenomenon has brought phage therapy back into focus as a way to counteract drug resistant pathogens and complement antibiotic treatment. Phages demonstrate very selective toxicity and therefore, when applied to living tissue, will leave cellular structures outside of their target unharmed. As a result of this trait, phages inflict less damage onto the patient’s healthy microbiota.

Ongoing Research:

While lacking in quantity, clinical trials and case reports involving phage therapy have shown promising results. The PhagoBurn Clinical Trial is a phase I/II study initiated in 2015 that is looking to assess the use of phage cocktails in treating Escherichia coli and Pseudomonas aeruginosa bacterial infections in burn wounds. In vitro experiments show that engineered phages are capable of selectively killing Methicillin-resistant Staphylococcus aureus (MRSA), an antibiotic resistant bacterium, which indicates great potential of phages in treating drug resistant infections. Successful case reports of phage treatment in patients suffering from antibiotic resistant infections furthers optimism for the incorporation of phage therapy in standard medical care.


Phage therapy does not come without its limitations.  The current major downfall of this treatment route is the significant deficit in double-blinded, Phase III clinical trials that have been published to date. Phase III clinical trials are necessary to determine how a new medical intervention compares to existing treatments; however, they often require thousands of participants, copious amounts of funding and can take years to complete. Phages are also limited in their application as it is difficult to administer these agents intravenously, limiting their use to infections located more superficially within the body such as localized wounds or lung infections like pneumonia. As a maturing treatment there is currently no standard framework for application of phage therapy in western medicine which can inhibit their ability to be incorporated into treatment in the future.

Future Directions:

Phage therapy is a promising contender as an antimicrobial intervention that can complement antibiotic treatment. As the realm of “personalized medicine” develops, phage cocktails will be able to be designed to match a patient’s specific disease. Given the pace of current scientific growth and social progress, in as short as a few decades, one may expect that phage therapy will be finding a predominant place in medical standards of care.


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Wright, A., et al., A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa; a preliminary report of efficacy. Clin Otolaryngol, 2009. 34(4): p. 349-57.

Chlamydia pneumoniae

By Elena Lonina, Xinlan Yang and Yueran Zhao,


Chlamydia pneumoniae, also known as Chlamydophila pneumoniae, is a human pathogen that causes acute respiratory diseases such as pneumonia and bronchitis. It is an obligate intracellular parasite, which implies that it needs to reside inside a host cell to grow. C. pneumoniae was first isolated in 1965 but was not proved to be a pathogen until 1983. School-age children are the most susceptible target and carrier of the bacteria, with mild or even no symptoms following the infection. Chlamydia infections are known to be community-acquired, which means that the disease can spread in a community if one individual is sick. Therefore, re-infections are common in the older populations given that they can be easily exposed to the pathogen in their daily lives and their symptoms may be more severe due to the existence of co-infecting bacteria or underlying diseases.


C. pneumoniae infections are associated with severe systemic infections and coronary artery and acute respiratory diseases. It is transmitted between human carriers with or without symptoms through secreted droplets from the respiratory system, such as by sneezing or coughing. C. pneumoniaemay incubate inside the human body for several weeks since its entry to the onset of symptoms. C. pneumoniae is biphasic, which means it has two forms during its life cycle: the elementary body (EB), which has decreased intracellular activity to minimize energy consumption, and the reticulate body (RB) which is metabolically active and engages in replication. Further, the bacteria are infectious as EB but are non-infectious as RB. Although the bacteria require obligate intracellular growth, the EB form can survive extracellularly while waiting to reach a new host. These EB are picked up by immune cells called macrophages (Figure 1), which are recruited when the host cells detect a bacterial invasion, and start working to take up the intruder within little sacs called vesicles. Inside of the vesicles, C. pneumoniae blocks the fusion of the vesicle they reside in to lysosomes, which carries deadly enzymes to the bacterium, to prevent being killed. Then, the EB matures to an RB inside the hijacked vesicle and starts its replication process. This bacterial infection cannot be characterized by a specific set of syndromes, but common symptoms include sore throat and loss of voice before it develops into pneumonia or bronchitis. Even when the infection appears to be mild, the clearing of the bacteria from the patients’ bodies appears to be slow.

Figure 1. Transmission electron micrograph showing Chlamydia pneumoniae’s Elementary Bodies (arrows) attaching to the surface of the macrophage (A) and, once inside the macrophage, they attach to the surface of the vesicles before differentiation into reticular bodies and replication (B). Source: Hahn et al., 2002.


C. pneumoniae is one of the most common pathogens that cause upper and lower respiratory tract infections. As mentioned before, this bacterium can be easily transmitted from human to human via tiny droplets spread over in the air. When someone has a C. pneumoniae infection within a community with high population density, the risk of infection becomes higher because there would be a higher number of potential recipients that could catch the pathogen, and thus the probability of a C. pneumoniae outbreak would be increased.

C. pneumoniae causes infections in people of all ages globally. Noticeably, there is a distinctive characteristic of this infectious disease, which is that patients who have been infected by C. pneumoniae recently are more susceptible to a reinfection. Moreover, the susceptibility of an individual is greatly impacted by a series of factors. To illustrate, research has shown the most frequent ages that people get the very first C. pneumoniae infection is within a range of 5-15. This is most likely due to the underdeveloped immune systems of children and teenagers. Other conditions such as aging, obesity, immunocompromising conditions and underlying diseases (such as AIDS and chronic pulmonary diseases) also increase susceptibility, especially in adults. These underlying conditions usually make reinfections more dangerous for adults.

Virulence factors

Given that C. pneumoniae is an obligate intracellular pathogen, its internalization into host cells is crucial for its maturation, replication, and dissemination – events that will generate host damage and define the disease. Nevertheless, any incoming pathogen will need to face the first mechanical barrier that will limit its translocation and invasion: the plasma membrane. Thus, it is not surprising that C. pneumoniaehas evolved different methods to invade its host and ensure its survival.

One example is OmcB, an adhesin (a molecule that mediates adhesion) that has shown to attach to specific molecules present only in host cell membranes. What is surprising, however, is that OmcB can have little differences in its structures and that these will allow for C. pneumoniaeto bind to different variants of these host molecules that are spread throughout different types of cells, conferring specificity to its attachment.

C. pneumoniae is even further able to induce more complex changes that will enhance its internalization. To illustrate, Pmp21 is also an adhesin, but this one binds to a receptor present in the host cell membrane. When the adhesin binds, it activates the receptor and signals the cell to change its structure and to extend arms around the pathogen binding to the receptor (Figure 2). This way, C. pneumoniae actively stimulates the cell to take it in.

Figure 2. Chlamydia pneumoniae binds to specific host membrane structures to begin the invasion. For example, some adhesins in the Elementary Body (EB) can bind to host receptors located in its plasma membrane and activate it (a). Receptor activation signals the cell to start extending arms around the receptor and bringing it inwards (b and c). Ultimately, a vesicle forms with the bacterium inside of it, where it can mature and start replicating (d). Source: Elena Lonina.

Another example of active stimulation is Cpn0473, which is an adhesin expressed in adhering EB and that binds preferably to cholesterol-rich regions in the host’s cell plasma membrane. What is interesting, however, is that the insertion of Cpn0473 in the plasma membrane will change the molecular composition of the plasma membrane. This change is usually associated with apoptosis of the host cell. However, the change initiated by Cpn0473 does not induce cell death, but instead induces endocytosis of the bacterium, which results in the internalisation of the bacterium similarly to what is observed in Figure 2.


Antibiotics are the optimal treatments for bacterial infections. Clinically, erythromycin and doxycycline are established treatments that can effectively clear the infection by inhibiting  bacterial protein synthesis, which means that it will not be able to create the molecules that will allow it to attach to the host, invade it, and mature. However, there are several side effects associated with these antibiotics, such as diarrhea, vomiting and headache. Other antibiotics such as tetracyclines and ofloxacin are applicable to adults, but they are restricted to children because of their potential to cause damage to their growing muscles, tendons, and skeletons. Usually, due to its high reinfection rick as mentioned above, a relatively large dose and long course of treatment is required to ensure the complete clearance of the pathogens.


Blasi, F., Arosio, C., and Cosentini, R. 1999. Chlamydia pneumoniae: Epidemiology. In Chlamydia pneumoniae: The Lung and the Heart. Edited by L. Allegra and F. Blasi. Springer Milan, Milano. pp. 52-61.

Fechtner, T., Galle, J.N., and Hegemann, J.H. 2016. The novel chlamydial adhesin CPn0473 mediates the lipid raft-dependent uptake of Chlamydia pneumoniae. Cell Microbiol 18(8): 1094-1105. doi:10.1111/cmi.12569.

Galle, J.N., Fechtner, T., Eierhoff, T., Römer, W., and Hegemann, J.H. 2019. A Chlamydia pneumoniae adhesin induces phosphatidylserine exposure on host cells. Nature Communications 10(1): 4644. doi:10.1038/s41467-019-12419-8.

Hahn, D.L. 2002. Chlamydia pneumoniae as a respiratory pathogen. Frontiers in Bioscience 7(1-3): e66. doi:10.2741/hahn.

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Moelleken, K., and Hegemann, J.H. 2008. The Chlamydia outer membrane protein OmcB is required for adhesion and exhibits biovar-specific differences in glycosaminoglycan binding. Molecular Microbiology 67(2): 403-419. doi:10.1111/j.1365-2958.2007.06050.x.

Mölleken, K., Becker, E., and Hegemann, J.H. 2013. The Chlamydia pneumoniae Invasin Protein Pmp21 Recruits the EGF Receptor for Host Cell Entry. PLOS Pathogens 9(4): e1003325. doi:10.1371/journal.ppat.1003325.

Paldanius, M., Bloigu, A., Alho, M., Leinonen, M., and Saikku, P. 2005. Prevalence and Persistence of <em>Chlamydia pneumoniae</em> Antibodies in Healthy Laboratory Personnel in Finland. Clinical and Diagnostic Laboratory Immunology 12(5): 654. doi:10.1128/CDLI.12.5.654-659.2005.

Vibrio vulnificus

By: Claudia Mangiola, Daniel Moses and Janina Ruffini 


Vibrio vulnificus is a Gram-negative bacterium responsible for the majority of seafood-associated deaths in the United States. As a natural inhabitant of warm oceans and estuaries, it is found in high concentrations in shellfish such as oysters and clams, which serve as the source of transmission when consumed or exposed to wounds. Incidences of V. vulnificus generally occur as isolated cases, although outbreaks affecting multiple states have been reported. 


Three biotypes with identical genotypes of pathogenic V. vulnificus have been identified and classified according to their biochemistry. Biotype 1 strains are found in salt water worldwide and are therefore the most common. They present the greatest concern to human health due to their large spectrum of symptoms and high mortality rate. Biotypes 2 and 3 are associated with farmed eels and freshwater fish in the Middle East and rarely cause severe infection in humans. The presence of V. vulnificus does not affect the taste or odor of contaminated seafood, making detection challenging. Consumption of this seafood results in gastroenteritis (inflammation of the stomach and intestines) accompanied by fever as well as septicemia (blood infection). Individuals with septicemia develop a fever, abdominal pain, hypotension and skin lesions on their extremities. This condition develops in 1 week and is fatal in up to 60% of cases. Handling contaminated seafood and exposing wounds to water containing V. vulnificus can cause skin infections. Patients with wound infections typically have a pre-existing lesion. The wound inflames and becomes very painful however they have a lower mortality rate. Necrotizing fasciitis, being the most severe form, is characterized by black bulbous protrusions, patchy discoloration, and scalding of the skin, similar to that caused by Streptococcus pyogenes depicted in figure 1. V. vulnificus infection can be diagnosed by detecting edema in the radiography of tissues and by performing blood cultures and Gram stains from lesions. 

Figure 1. This man’s leg is severely infected causing necrotizing fasciitis. It shows hemorrhagic bullae (black bulbous protrusions), patchy discoloration, and scalding of the skin. Surgery was necessary to help clear the infection. Source: Smuszkiewicz, 2008.


V. vulnificus is more prevalent in the USA along the coastline of the Gulf of Mexico. While bacteria can survive in water temperatures between 9℃ – 31℃, they prefer warmer waters above 18℃, predominantly in the months between April-October.  Infection occurs from ingestion of uncooked contaminated seafood such as oysters. Of those infected, there is a 40-60% mortality rate, mostly caused by septicemia. The CDC estimates that infection rates are over 200 cases per year. Although a more rare disease, risk factors prior to infection include alcoholism, primary septicemia, liver disease and any chronic diseases. 

Virulence factors

Infection of V. vulnificus results in symptoms within 24 hours. That being said, the bacterium is able to evade the immune response and cause disease very quickly due to its virulence factors. Virulence factors are molecules produced by bacteria which help to colonize a host, or help it evade the host’s immune system allowing it to persist and cause damage. The virulence factors of V. vulnificus allow bacteria to survive acidic environments, evade the innate immune response and acquire nutrients from the environment. This is accomplished through the polysaccharide capsule and an iron acquiring mechanism unique to V. vulnificus.

Once the bacterium enters the bloodstream, the innate immune system responds with the protein complex referred to as complement proteins. These will bind to the bacterium and cause an immune cell to engulf it. This is actually avoided in V. vulnificus because of the polysaccharide capsule which does not allow these proteins to bind, thus avoiding being taken up by macrophages (immune cells) (Figure 2). Another essential virulence factor is iron acquisition. This has been shown to enhance growth and to compromise the immune response. This is accomplished through a unique mechanism in V. vulnificus which uses a protein encoded in its genome that take iron from red blood cells. V. vulnificus has the ability to regulate these virulence factors with quorum sensing, which is the up or down regulation of gene expression in response to cell density and sensory signals. Quorum sensing is used to control gene expression of proteins that acquire iron from red blood cells.

Figure 2. This is a cell of V. vulnificus shown with its many virulence factors. The complement system and macrophages do not have any effect on the invading cells because of the polysaccharide capsule. Also shown are the siderophores for iron acquisition, pili for adhesion and colonization, the flagella for motility, the heme receptor and lipopolysaccharides (LPS) on Vibrio’s surface. Source: Janina Ruffini.

Treatment and Prevention 

Treatment of V. vulnificus is strongly dependent on the type of infection, whether it is septicemia, a wound infection, or gastroenteritis. A variety of antibiotics have been shown to be effective against V. vulnificus. These are given orally and intravenously in certain combinations. It is imperative that people who suspect a V. vulnificus infection seek immediate help for septicemia since survival is dependent on how quickly treatment is received. 

In cases of wound infections, antibiotics are usually ineffective because of thrombosis (clots) in the blood vessels near the infection site, and the antibiotics do not reach the infected tissues. Often surgery is required to remove the bacterial burden and damaged tissues, sometimes even amputation of limbs is necessary to save the patient. 

Gastroenteritis, unlike septicemia and wound infections, often goes unreported. Symptoms include fever, diarrhea, abdominal cramps, nausea, and vomiting but tends to resolve itself. Replacement of fluids and rest are the ideal treatment in this case. 

The CDC has reported a list of preventative measures one can take to avoid V. vulnificus infection, which boils down to cooking shellfish thoroughly. 


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Mycobaterium tuberculosis – Inuit communities (ongoing)

By: Katerina Lazaris, Anne McGrath, Katie Mallett

Outbreak of Tuberculosis in Inuit communities of Canada


Tuberculosis (TB) is a contagious, airborne disease that commonly infects the lungs. It often affects socioeconomically disadvantaged communities, where nutritional deficiency is common. In Canada, there is a long history of a disproportionately large number of cases of TB in Inuit communities compared to the rest of Canada (figure 1). In fact, as of 2018, the average annual rate of TB among the Inuit people in Canada was more than 290 times higher than Canadian-born non-Indigenous people. TB can be life-threatening if not treated promptly and therefore poses a serious risk in Inuit communities that can be characterized by inequitable access to health care and unfavourable living conditions.

Figure 1: Tuberculosis incidence rate per 100,000 people by Canadian province or territory in Canada in 2016. Source: Adapted from Vachon, J et al. “Tuberculosis in Canada, 2016.” Canada communicable disease report = Releve des maladies transmissibles au Canada vol. 44,3-4 75-81. 1 Mar. 2018, doi:10.14745/ccdr.v44i34a01

Description of Tuberculosis:

TB is an infectious disease caused by the bacterium Mycobacterium tuberculosis. M. tuberculosis is an airborne pathogen that colonizes and grows most commonly in the lungs (due to the high levels of oxygen) but can also infect other parts of the body. TB infection can either be latent, where it is not contagious, as the immune system inhibits proliferation, or active, where bacteria counts are high enough to cause symptoms. Symptoms include coughing, decreased appetite and unintentional weight loss, fever and night sweats, fatigue and chest pain, among others (figure 2). Coughing allows the bacteria to exit the body via droplets, transmitting the disease very effectively. Those who are most susceptible to contracting TB include HIV+ individuals, people living in crowded areas, drug abusers and people with poor nutrition. Many of these risk factors are associated with low socioeconomic status.   

Figure 2: Symptoms and transmission of Mycobacterium tuberculosis. Illustration by Katerina Lazaris. Source: Adapted from Timonina, Iryna. “Symptoms of Tuberculosis.” Dreamstime,


TB was a leading cause of death in Indigenous communities, and until the 1950s, rates of infection were equal to those in the developing world. Incoming European settlers brought TB to Canada in the 1700s, which spread across Indigenous communities, as they had never been exposed to this disease. Residential schools were particularly vulnerable to infection due to malnutrition and confinement.  High rates of TB have continued to persist in the Inuit community, perpetuating the history of neglect Canada has had for Indigenous people. Canada has an annual 1,700 cases of TB. These 1,700 cases are found almost exclusively in marginalized groups, including First Nations and Inuit people. The alarming discrepancy can be accounted for by socioeconomic factors that Aboriginals are subjected to in Canada.

Overcrowded living situations increase the risk of transmitting the infection. Currently, 52% of Nunavut’s population live in social housing, with 72% of them being overcrowded. It can be common to find 20 people living in a 4-bedroom house. An airborne pathogen like TB can easily be transmitted in these close quarters. This is exacerbated by poor ventilation, which is common in these homes. Malnutrition is another risk factor of TB. For this reason, food insecurity increases susceptibility to this disease. On average, food prices are twice as high in Nunavut as those in southern Canada. Scattered populations, far from major transportation hubs make for high shipping costs. Food is often limited in choice and may be of poor quality or void of nutrients. Smoking also greatly increases the risk of contracting respiratory infections, such as TB. Approximately 61% of Nunavut’s population smoke, which is much higher than the Canadian average. Poor access to health care allows for infections to persist for longer, which increases the chance of others being infected. When health care is an option, people often feel unsafe going to a hospital or nursing centre.

Dr. Anna Benerji, a specialist on pediatric infectious and tropical diseases, suggests respiratory syncytial virus (RVS) may be another risk factor. Inuit babies have the highest rates of RSV in the world. Currently, the government of Nunavut only provides antibodies for RSV as a preventative measure for high-risk babies. Benerji believes that scarring or damage to the lungs by RSV at a young age may leave individuals more susceptible to future TB infections. However, the relationship between TB and RSV must be studied further to confirm a connection.

It’s important to note the impact of colonialism on this complicated issue. In the past, the solutions imposed to combat TB were cruel. Many were forcibly removed from their homes for treatment. This, understandably, has left many Aboriginal people reluctant to undergo TB treatment, screening, and vaccination. As mentioned previously, delayed treatment increases the risk of transmission. Overcoming this stigma associated with the past cruel treatment of patients may help reduce spread of TB. This, paired with improved living conditions and food security, will hopefully decrease rates of infection in the Inuit community.

Measures Taken:

Prevention: Amongst the measures taken to reduce the cases of TB in Inuit communities is spreading awareness in the community through education programs that increase understanding of TB. These include risks, causes and routes of transmission. A community based, youth focused, education initiative was implemented in four different communities in Nunavut which resulted in uptake of knowledge among participants. Furthermore, TB nurse educators provide an avenue to educate and train staff, better equipping the community to treat and prevent TB infection. It is important to note that new staff are being trained in TB care. Due to a limited number of healthcare resources, it is more efficient to train new staff in TB care rather than training existing health care staff. Shifting existing staff to the efforts to combat TB would lead to vulnerabilities in other areas of healthcare.

Detection: In order to detect TB infection as early as possible, individuals of the community are screened for infection. Early detection will prevent the progression of the disease. The sooner the infection is detected, the less severe the symptoms.

Treatment: In addition, individuals with active cases of TB are isolated in their homes to prevent disease transmission to healthy individuals. Considering TB is an airborne pathogen, setting up a quarantine protects others from infection. As for treatment, patients with active TB undergo quadruple therapy which involves taking a combination of 4 different drugs: Ethambutol, Isoniazid, Pyrazinamide and Rifampin. This treatment occurs with directly observed therapy; a method of drug administration in which someone watches the patient as they take their medication. This ensures that treatment plans are being followed to successfully reduce the incidence of TB. Educated staff and directly observed therapy are very important in TB treatment because these measures ensure that the development of Multi-drug resistant TB (MDR-TB) is limited. MDR-TB, which is defined as TB bacteria that are resistant to at least isoniazid and rifampin, can occur because of administration of improper treatment regiments and failure to ensure that the patients properly complete their treatment. This can be dangerous because it complicates TB treatment although it can be managed by properly controlled treatment.


In light of the historically high rates of TB in Inuit communities, the government is taking action to prevent future outbreaks.  A program that educates and encourages the Inuit people against nicotine use has been started in order to decrease smoking. Additionally, in order to improve the Nunavut health care system as a whole, which in turn advances TB treatment programs, digital X-rays as opposed to formerly used film X-rays have become the norm for diagnosis, as digital X-rays take a fraction of the time to send to other locations. This accelerates the time it takes for a patient to receive treatment, ultimately curbing the spread of TB. A community engagement strategy is also being developed to demarginalize people who are battling TB so they can receive the treatment they need. Despite these positive initiatives put into place in response to the TB prevalence in Inuit communities, funding for programs and medical equipment such as what is needed for screenings is still a big limiting factor in improving the TB outbreaks amongst the native population in the North. Finally, in response to Canada’s long history of neglect of indigenous people’s health, Justin Trudeau has acknowledged and apologized for this marginalization. Furthermore, the federal government has vowed to eradicate TB in Inuit communities by the end of the next decade.   


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Oudshoorn, Kieran. “Nunavut TB rates remain high despite community testing.” CBC, 11 Jun 2019, Accessed 13 November 2019.  

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Patterson, M, et al. “Addressing Tuberculosis among Inuit in Canada.” Canada Communicable Disease Report, vol. 44, no. 3, ser. 4, 1 Mar. 2018. 4.

Picard, André. “In Canada, Tuberculosis Exists as a Symptom of Social Inequity.” The Globe and Mail, 26 Mar. 2018,

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Vachon, J et al. “Tuberculosis in Canada, 2016.” Canada communicable disease report = Releve des maladies transmissibles au Canada vol. 44,3-4 75-81. 1 Mar. 2018, doi:10.14745/ccdr.v44i34a01

Cronobacter sakazakii

By Kathryn Landry, Natalia Lorenc and Fiona Chan Pak Choon


Cronobacter sakazakii is a rod-shaped Gram-negative opportunistic pathogen most commonly infecting infants and people with weakened immune systems. It was first isolated in 1980 by JJ Farmer III, who named the species Enterobacter sakazakii. In 2007, it was reclassified as C. sakazakii. This food-borne pathogen is capable of surviving in dry environments such as powdered infant formula. 

Figure 1. Bacterial colonies of C. sakazakii on a Petri dish after a three day incubation at 25 °C on trypticase soy agar. Source: Public Health Image Library, Center for Disease Control, Dr. J.J. Farmer (1978).


C. sakazakii is primarily transmitted by the consumption of contaminated foods such as powdered infant formula (PIF), cereal, dried herbs, and pasta. PIF is the most frequent vector and contamination may be caused in the factories, when being prepared at home, or through improper storage. Contamination occurs in both hospitals and at home.

Although bacterial infection of this sort is unusual, it is quite harmful once it enters the body under the right conditions. When children are born, their immune systems are very weak, which makes it harder for them to fight pathogens. Infants affected by maternal disease, are premature, or had a traumatic delivery are more susceptible to infection. On the contrary, adults have a more developed immune system that is capable of eliminating the bacterium. If an infant survives an infection by C. sakazakii, delayed brain development and other neurological disorders are frequent. Additionally, infections often result in sepsis, meningitis, which is a brain inflammation, or necrotising enterocolitis, an intestinal infection. Symptoms of the disease include loss of appetite, fever, and irritability. 


Cronobacter sakazakii prevails in low-weight neonates and premature babies, whose immune systems are underdeveloped. It is also common in immunocompromised elderly, although individuals of all ages may be infected. This pathogen was first identified in England from an infected patient. In 1958, two neonates died from C. sakazakii induced meningitis. Since the first identification, cases have increased. In 1998, an outbreak in Belgium killed 12 neonates in intensive care. 

Currently, C. sakazakii infects four to six infants in the United States every year. In 2013, the estimated mortality rate was 80%. The rarity of cases creates difficulties in determining these statistics. 


Since C. sakazakii is mainly a foodborne pathogen, it enters the host’s digestive tract via the mouth and then reaches its target site in the intestine. The bacterium adheres to the intestinal epithelial cells with the help of a glycoprotein called fibronectin (Figure 2A). In the host, fibronectin is found in the blood plasma and on cell surfaces. It helps mediate wound healing due to its ability to join 2 cells together by binding to both of these cells. By binding to the fibronectin present on the surface of intestinal epithelial cells, the pathogen adheres more strongly to the host tissue. The bacterium can also bypass the epithelium in newborns due to their underdeveloped tight junctions found between cells (Figure 2B). These junctions normally prevent such invaders to enter the bloodstream.

Once attached to its target cells, C. sakazakii invades the latter in order to enter the bloodstream, replicate, and proliferate. The bacterium contains 2 outer membrane proteins (Omp), OmpA and OmpX, which have an essential role in the invasion of intestinal cells (Figure 2A). After invading the intestinal cell, the pathogen moves across the cell before being released into the bloodstream via exocytosis – the transport of vesicles containing cellular components from the interior to the exterior of the cell. Once in the bloodstream, C. sakazakii travels to the blood-brain barrier before infecting the endothelial cells making up the barrier (Figure 2C). This causes meningitis, the inflammation of membranes surrounding the brain and the death of brain cells. OmpA and OmpX play a role in this secondary invasion, but their mechanism remains unknown.

C. sakazakii can also evade the host’s immune system by invading and replicating within macrophages – white blood cells that engulf and digest bacteria. It is believed that C. sakazakii possesses the ability to produce an enzyme called superoxide dismutase. This enzyme detoxifies potent compounds called reactive oxygen species (ROS) that are synthesized by macrophages to help digest bacteria. ROS can no longer degrade the pathogen and thus the pathogen survives and replicates. In addition, the pathogen is thought to produce enterotoxins that have yet to be determined.

Figure 2. The pathway of infection and virulence mechanisms of C. sakazakii. A) Action of fibronectin and virulence factors, OmpA and OmpX, in the invasion of the pathogen into intestinal epithelial cells. B) Pathogen infiltration to the bloodstream due to lack of tight junctions. C) Pathogen crossing the blood-brain barrier to infect brain cells. Source: Fiona Chan Pak Choon


There are currently no available vaccines against C. sakazakii, but C. sakazakii is susceptible to several antibiotics including β-lactams, which inhibit the production of peptidoglycan, an important component of the bacterial cell wall. However, C. sakazakii contains several genes and mechanisms of antibiotic resistance, reducing the ability of the antibiotics to eliminate the infection. C. sakazakii has several efflux pumps, which remove the antibiotics from the cytoplasm and are therefore unable to locate their target and inhibit or kill the bacteria. In order to reduce the formation of antibiotic resistance, it is important to take the entire regimen of antibiotics the doctor prescribes.


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Farmer JJ, Asbury MA, Hickman FW, Brenner DJ, and The Enterobacteriaceae Study Group. 1981. Enterobacter sakazakii: A new species of “Enterobacteriaceae” isolated from clinical specimens. International Journal of Systematic and Evolutionary Microbiology. 30(3): 583

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Bartonella henselae

By: Aaron McCall, Audrey Roberge, Brett Moffit


Bartonella henselae is the bacterial species that causes Bartonellosis, Cat Scratch Disease (CSD), or Cat Scratch Fever in humans. This species of Bartonella is a facultative intracellular Gram-negative bacteria that commonly infects cats and less commonly dogs. As it’s common name suggests, Cat Scratch Disease is contracted through the scratch or bite of an infected cat (Figure 1).

Figure 1: Summary of the B. henselae life cycle showing that transmission to cats is achieved commonly by the cat flea. Consequently, humans get infected when scratched or bitten by an infected cat and possibly directly from the blood sucking vector.  (Source: CDC(2015)

The reservoir host for Bartonella henselae  are cats which are therefore asymptomatic carriers. Cats contract B. henselae upon being infested with the common cat flea, Ctenocephalides felis  where they reside in the gut and are expelled onto the cat’s skin via flea droppings. The cat becomes infected upon grooming itself which causes the bacteria contaminated flea feces to spread to its mouth and claws. Hence, transmission to humans results from the bite or scratch of an infected cat resulting in the inoculation of the flea feces and consequently the bacteria, into the open wound. Other potential vectors include additional blood sucking insects and arthropods such as ticks, lice and biting flies, namely the sand fly.

B. henselae causes disease primarily given the fact that it is able to evade the immune system by establishing an intracellular infection, as it is a facultative intracellular pathogen. Infection begins once the bacteria get inoculated through a bite or scratch wound and initially infect macrophages, the white blood cells that protect the body by  “eating” pathogens. This allows the bacteria to subsequently infect the cells of the blood vessel lining, the endothelium. During this stage of infection, generally no symptoms are observed in immunocompetent individuals; however, bacillary angiomatosis is seen in immunocompromised patients. In this case, the bacteria trigger the endothelium lining cells to divide continuously, as well as block apoptosis, the ability for cells to self destruct. Therefore, resulting in the massive proliferation of the endothelium cells causing tumor-like structures that outgrow giving the appearance of papule lesions on the skin of the individual. Following infection of the endothelium, B. henselae can then infect red blood cells– also called erythrocytes– allowing them to establish a chronic infection as they are able to go undetected since red blood cells do not express MHC 1, an immune system activating signal protein that indicates that a cell has an intracellular pathogen. With the absence of MHC 1 the cytotoxic pathway of the adaptive immune system is not activated and therefore cannot effectively kill the intracellular pathogen. Infection in the blood also provides the bacteria with a highway by which it can travel to infect various organs. A common site of infection are the lymph nodes resulting in lymphadenopathy, which is severe regional inflammation of the lymph nodes. This is caused by the ongoing activation of  the adaptive immune response as macrophages continually present B. henselae antigens to naive T cells,T cells who have not yet differentiated into a specific immunological role, either Killer T cells or  Helper T cells. The continual presentation of B. henselae antigens to naive T cells triggers them to differentiate in order for the appropriate adaptive immune response to take place. However, since B. henselae establishes a proliferant intracellular infection of macrophages, this results in overwhelming the naive T cells to differentiate at a rate of which the lymphoid tissue can not keep up, resulting in hyperplasia of the lymph nodes, increasing the size of the tissue to compensate for the high demand of naive T cell differentiation. It has also been suggested that bartonella effector proteins (BEPs)  also play a role in the presentation of this symptom, which will be discussed in greater detail in the virulence section. Another possible organ where infection takes place are the cells of the heart. This results in endocarditis and myocarditis– an inflammation of the heart– causing malfunctioning of the heart as it becomes more strenuous to pump blood throughout the body. This inflammation is clinically distinguished by the presence of heart murmurs.


The most common species of Bartonella found in infected cats is B. henselae. Within B. henselae, there are two different genotypes known to infect cats: Houston-1 (type 1), and Marseille (type 2). Type 1 B. henselae are more prevalent in Asia, while type 2 are found more commonly in western United States, western continental Europe, the United Kingdom, and Australia. Worldwide, infections of B. henselae are found more often in warm humid areas than in colder climates. However, regardless of the genotype that is most prevalent within a given country, the strains isolated from infected humans is most often type 1. The age and lifestyle of the cat also affects the probability of infection; young cats under the age of 1 year old and stray or feral cats are more likely bacteremic. This means that young, stray, or feral cats have a high probability of carrying or having this species of bacteria in their blood. Conversely, as cats get older, their probability of being seropositive for B. henselae increases. This is because as the young bacteremic cats age, their immune systems fight the infection and develop specialized antibodies designed to destroy the B. henselae cells present in the blood. After the cat recovers from the infection, the antibodies produced will persist in the blood and cause seropositivity. Antibody persistence is a part of acquired immunity and will help the cat fight off any subsequent infections of B. henselae more quickly and more efficiently.

Virulence Systems:

B. henselae employs specialized systems, called virulence factors, that help it colonize a host, infect the host’s cells, spread, and cause damage. The bacteria will infect the primary niches, which are the cells that help it migrate to the blood (macrophages and endothelial cells). The mechanism of this step is unclear, but the bacteria become competent after a priming period inside the primary niche, during which it stimulates inflammation but inhibits programmed cell death. It will then adhere to erythrocytes and force the erythrocyte to deform (with a protein called deformin) and internalize it, despite the erythrocyte’s usual lack of endocytic activity (internalizing something from outside the cell). Once in the erythrocyte, B. henselae can protect itself within a vacuole in the cell. This is also a potent virulence factor because it allows the bacteria to hide from the host’s immune defences. They also can evade the host’s immune system by hiding or modifying pathogen-associated molecular patterns which are patterns that the host would recognize as foreign bacteria. Once it has established itself in the blood, B. henselae will activate other virulence factors that are mostly involved in migrating from erythrocytes into other tissues. These mechanisms are poorly studied, although the bacteria express the same proteins that other types of bacteria employ, so these proteins likely are involved. When in other host cells, B. henselae use a type IV secretion system (T4SS) which delivers toxins directly to the host’s cells to release specific proteins called bartonella effector proteins (BEPs) that will cause the human host to produce a pathologic amount of erythrocytes so that the bacteria has more cells to colonize, as well as damaging the structure of many host cells to make them easier to invade. Other virulence factors cause hyperactivation of the adaptive immune system in lymph nodes (Figure 2), causing an intense immune response that will damage the host and direct tissue damage, especially to the heart, which is likely mediated by BEPs.

Figure 2: Enlarged lymph node. B. henselae will migrate through the blood to lymph nodes and induce a local immune response, resulting in inflammation (Source: CDC(2015)


Generally, Bartonellosis subsides on its own with no medical intervention needed. A two-week treatment of Azithromycin, an antibiotic, is sometimes used to treat and diminish the time of lymphadenopathy presentation.  A much lengthier treatment is required for more severe cases, especially in immunocompromised individuals, with an antibiotic treatment that can last up to six weeks. In this case, antibiotics of choice maybe be doxycycline, erythromycin and rifampin or any combination of the three medications. In cases where a patient has reached endocarditis, heart failure medications are also administered to manage the cardiac symptoms and valve replacement may be recommended.


Alexandre Harms, C. D. (2012). Intruders Below the Radar: Molecular Pathogenesis of Barontella spp. American Society for microbiology. Retrieved from:

Angelakis, E., & Raoult, D. (2014). Pathogenicity and treatment of Bartonella infections. International Journal of Antimicrobial Agents, 44(1), 16–25. doi: 10.1016/j.ijantimicag.2014.04.006 

CDC. (n.d.). Bartonella Infection (Cat Scratch Disease, Trench Fever and Carrion’s Fever). Centers for Disease Control and Prevention. Retrieved from:

Oskouizadeh, K., Zahraei-Salehi, T., & Aledavood, S. (2010). Detection of Bartonella henselae in domestic cats’ saliva. Iranian journal of microbiology, 2(2), 80–84. Sykes, J. E. (2014). Bartonellosis. In C. a. Diseases, Jane E Sykes (pp. 498-511). St Louis: Elsevier.

Increasing antibiotic effectiveness against Pseudomonas aeruginosa, a multidrug resistant pathogen, using a compound isolated from tea leaves

Béatrice Bédard-Lepage, Erika Levoy and Rowena Groeneveld

Pseudomonas aeruginosa is a Gram-negative non-fermentative bacterium, meaning it has a thin peptidoglycan layer and is not able to ferment glucose to alcohol. It is an opportunistic pathogen, which means it is usually harmless until the infected person is weakened. P. aeruginosa causes infections difficult to treat in wounds, burns, respiratory tract and bloodstream and was often associated with outbreaks in the past years. In fact, it is responsible for a lot of pneumonia infections acquired in hospitals, because it targets immunosuppressed or artificially breathing patients. Sadly, this pathogen has high rates of morbidity and mortality because it is becoming more and more resistant to multiple antibiotics. For more information on P. aeruginosa check out the article describing this pathogen, (link:

Usually, we use an antibiotic called aztreonam (Figure 1) to treat P. aeruginosa infection. Aztreonam is a synthetic molecule that contains one 4-membered cyclic amide ring called β-lactam. Unfortunately, many strains of P. aeruginosa are evolving to produce β-lactamase, an enzyme capable of breaking the β-lactam ring in the aztreonam, which cancels the effect of the antibiotic. P. aeruginosa bacteria also have efflux pumps, which are in their membrane and can pump any antibiotics inside the bacteria out before they do any damage. An idea to restore the effect of the antibiotic is to use the aztreonam in combination with another compound, either a β-lactamase inhibitor, or any other molecule that could protect aztreonam or help the antibiotic get inside the bacteria to kill them.

Figure 1: Molecular structure of Aztreonam. Source: Rowena Groeneveld.

The compound that we are interested in today to increase the effects of aztreonam is epigallocatechin gallate, shortened to EGCG (Figure 2). EGCG is a molecule known as a polyphenol and is found in plants that are used to produce tea, such as Camellia sinensis (Figure 3). EGCG is known to be slightly antimicrobial (damaging to bacteria) by itself, but in a recent study, Betts et al.,  carried out an experiment to determine if EGCG could restore the activity of aztreonam against the resistant strains of P. aeruginosa. They came out with interesting findings in their paper Restoring the activity of the antibiotic aztreonam using the polyphenol epigallocatechin gallate (EGCG) against multidrug-resistant clinical isolates of Pseudomonas aeruginosa and the relevant points of their experiments are discussed below.



Figure 2: molecular structure of EGCG. Source: Rowena Groeneveld.

Figure 3: illustration of C. sinensis. Source: Rowena Groeneveld.


The first step the scientists took was to look at how much of the antibiotic aztreonam was needed to stop the various strains of P. aeruginosa from growing. Then, they did the same thing with EGCG, and finally they combined the two. They found that with both EGCG and aztreonam combined they needed a lot less of each to stop the bacteria from growing than they would if they used them alone. This means that the two together had a much larger effect than either on its own.

After that, they used the two most antibiotic resistant strains of P. aeruginosa and looked at whether EGCG and the antibiotic could kill the bacteria by seeing if the number of bacteria decreased over 24 hours. Alone, neither was successful, but together they managed to reduce the number of bacteria by a factor of around ten million by the end of the 24 hours.

One thing that was not very clear, was how the EGCG was improving the effect of the antibiotic. The next step the scientists performed was to look at whether EGCG was causing the bacteria to take up, or consume, more of the antibiotic. This would mean more aztreonam can enter the bacterial cell and do more damage before the bacteria can destroy it or get rid of it. They used a fluorescent compound called ethidium bromide and measured how much the pathogen was taking up by itself, and how much it took up when there was EGCG in the mixture. EGCG not only increased the amount of ethidium bromide that was taken up, but also the speed at which it happened.

Now that they could see that EGCG helped the antibiotic destroy the pathogen, they wanted to make sure that it would not damage the host (us). To do this, they grew human skin cells in the presence of EGCG and looked at how many of the cells died. They tested concentrations of EGCG needed to inhibit the growth of 90% of the P. aeruginosa strains and found that after 4 hours at the highest concentration, less than 10% of the human skin cells died.

Next, they did something similar in a species of moth known as Galleria mellonella. However, they also looked at how the antibiotic aztreonam affected the insects, as well as whether the combined effect of EGCG and aztreonam harmed the moths. They found that none of the moths died, even when they used nearly one-hundred times the normal concentration of EGCG. They also checked the moths for melanization. Melanization is an increase of melanine (the skin pigment that allows us to tan to protect ourselves from the UV rays) caused by the immune response of insects. The presence of melanine can be used as an indicator of minor toxicity, and they found no significant increase in melanin for any of the compounds.

After this, they did almost the exact same experiment, but first they infected the moths with P. aeruginosa. They found that when they combined aztreonam with EGCG, a largest amount of moths survived than if they only treated them with aztreonam. This means that the EGCG restores the ability of the antibiotic to kill off the bacteria in the animal model (the moths), but further tests would need to be done to determine if this will work in humans.

Importance of the findings

In a world facing increasing antibiotic resistance, the fact that EGCG can significantly boost the effectiveness of an antibiotic that was once ineffective on its own, comes as a large step in the right direction. What may be even more important, is that although the effectiveness of the antibiotic against P. aeruginosa is increased, the combination with EGCG does not increase the overall toxicity to the human body. This means that this method may be used in the future as a successful form of treatment against P. aeruginosa.

However, P. aeruginosa is not the only bacteria that resists antibiotics nowadays. For example, penicillin resistant strains of Streptococcus pneumonia have appeared, a well-known bacterial pathogen that causes pneumonia and other infectious diseases. The continued threat of antimicrobial resistance will require new ideas, such as the one suggested in this paper, or else humans will once again be threatened by basic bacterial infections.

By continuing to administer unspecific antibiotics, humans may once again live in the age where simple infections like pneumonia could be life threatening.

Despite this, stopping the use of antibiotics is simply not an option in today’s society. Humans have become too dependent on this simple and quick fix to a wide array of infections. Stopping the use of prescribed antibiotics would only slow the progression of microbe’s resistance to antibiotics. It would not provide a solution for the microbes which have already developed resistance. This article proposes a promising solution, wherein antibiotics are still being used, but the period of time in which they are useful is lengthened by combining them with other compounds.

It is novel techniques such as this combination that may allow humanity to stay one step ahead of the ever evolving microbes. Further studies are still needed to discover other combinations of compounds and antibiotics, but if one compound was found in something as common as green tea, it is likely that others are just waiting to be found.


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Betts JW, Hornsey M, Higgins PG, Lucassen K, Wille J, Salguero FJ, Seifert H, La Ragione RM. 2019. Restoring the activity of the antibiotic aztreonam using the polyphenol epigallocatechin gallate (egcg) against multidrug-resistant clinical isolates of pseudomonas aeruginosa. Journal of Medical Microbiology. 68(10):1552-1559.

Buehrle DJ, Shields RK, Clarke LG, Potoski BA, Clancy CJ, Nguyen MH. 2016. Carbapenem-Resistant Pseudomonas aeruginosa Bacteremia: Risk Factors for Mortality and Microbiologic Treatment Failure. Antimicrobial Agents and Chemotherapy. [accessed 2019 Nov 11]; 2016;61(1):e01243-16. doi:10.1128/AAC.01243-16

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Haemophilus parasuis


Haemophilus parasuis is a Gram-negative, rod-shaped bacterium that causes Glasser’s disease in pigs. While H. parasuis is often found in swines’ upper respiratory tract (URT) as part of their normal microbiota, stressed and immunocompromised pigs are susceptible to infection and subsequent disease, which is characterized by pneumonia, fibrinous polyserositis, polyarthritis and meningitis. In 1910, Glasser was the first to describe the bacterial infection, and by 1943, it was evident that the causal pathogen was H. parasuis. Since then, worldwide outbreaks of Glasser’s disease are on the rise, and infection afflicts almost every large-scale swine production system. H. parasuis is also implicated in increasing the morbidity and mortality of other viral infections, such as Porcine Reproductive and Respiratory Syndrome Virus.


H. parasuis is most commonly transmitted via direct contact, but is known to also be transferred via aerosol inhalation. Although not well characterized, H. parasuis is thought to infect the pig when its immune system is compromised or when the host experiences stress. The bacteria first attach to and colonize the mucosa of the nasal cavity. Once inside the bloodstream, H. parasuis targets the epithelial cells lining the chest, abdomen, brain cavity, heart sac, and joints (serosal membranes). Once the bacteria adhere to the epithelial cells, it induces cell death, which in turn releases signaling molecules that induce the host’s immune system. This will then cause inflammation and can lead to severe inflammatory injuries, such as swollen joints and purple extremities. Currently, there have been 21 different serovars, variations of H. parasuis with different surface proteins, classified. The different serovars range in virulence with the most virulent being able to invade endothelial cells. However, this invasion is not required for disease to occur.

H. parasuis can cause three clinical forms of Glasser’s disease—a sporadic form in young pigs, a second form characterized by sub-capsular kidney bleeding and sudden death, and a third form as a secondary agent in infections of Circovirus and virus causing swine Reproductive and Respiratory Syndrome. At the beginning of the acute form, pigs often show symptoms of increased body temperature of above 40 °C, lethargy, coughing, anorexia, and incoordination. If H. parasuis crosses the endothelial cells lining the blood-brain barrier and reaches the central nervous system, it can cause meningitis, which is characterized by inflammation of the sacs that surround the brain. This disturbs the nervous system and can cause neurological clinical signals such as tremors and convulsions. If the disease progresses to chronic form, then chronic arthritis and severe fibrosis can occur and stunt growth rate.

Figure 1: Three months old piglet that died due to Glasser’s Disease. It is exhibiting severe inflammation of the peritoneum (serous membrane lining the cavity of the abdomen and covering the abdominal organs) with accumulation of fluid in the abdominal cavity. (Source: International Journal of Veterinary Sciences and Animal Husbandry, S. Jyoti, R. Nepal, Dr. A. Thapa, Dr. S. Rimal, 2019)  


H. parasuis infection often occurs when an animal is purchased from an infected herd, thus introducing the bacteria to an unaffected herd (Figure 2). An infected herd is susceptible to an infection by a different serovar of H. parasuis because infection by one serovar does not provide immunity towards another serovar of H. parasuis. Therefore, a herd that was previously infected by one serovar can become infected by a different serovar of H. parasuis. The introduction of the new serovar occurs when a pig infected with the different serovar is brought into the herd. For example, a herd that was infected with serovar 1 does not have immunity towards serovar 2. If a pig infected with serovar 2 is introduced to this herd, then the pigs of the herd can become infected with serovar 2. When infection happens, animals of all ages are susceptible of contracting the disease, possibly leading to an outbreak. During an H. parasuis infections outbreak, infection rate of adults can reach 15% and young pigs 50%. 

Piglets are often the most afflicted with Glasser’s disease as infected mothers can transfer the bacteria through their breast milk. Piglets colonized by pathogenic variants will become carriers of the disease, but are immune. This is because their immune systems are able to develop while receiving immune protection from proteins in the mother’s milk. These animals will later carry the disease, but will not exhibit any observable symptoms. However, piglets that are not colonized by pathogenic serovar are highly susceptible to infection when they stop suckling. Since their developing immune systems have not been exposed to the pathogenic H. parasuis, the piglets are not able to ward off infection, leading to high rates of Glasser’s disease at the age of 5 to 6 weeks.

Figure 2: Illustration showing a possible case of transmission of H. parasuis. Source: J. Dujardin, 2019.


During infection, H. parasuis firstly invades the lung epithelium using a variety of virulence factors. As the first step in this process, the bacteria adheres to the host epithelium. This is facilitated by fimbriae, which are adhesion proteins on the bacterial surface. Secondly, H. parasuis must avoid the host’s immune system, which has cells trying to engulf and process the bacteria. For example, alveolar macrophages are innate immune cells located in the lungs’ alveoli and they constantly pick up bacteria to try and identify pathogens. When they find an invading microbe, macrophages will initiate an innate immune response. In order to circumvent these cells, H. parasuis has two virulence factors—a capsule and imitation of host cells’ surfaces. The capsule is a protective cover that is part of its outer membrane and protects the bacteria from most host immune responses, including engulfment by macrophages. All host cells are covered in sialic acid; therefore, H. parasuis mimics this by sialylation of their capsule layer. By having this virulence factor, the bacteria evade digestion. H. parasuis does this in an attempt to delay macrophage activity and, ultimately, the immune response.

If the macrophage is successful in engulfing H. parasuis, the cell still has to kill the bacteria via the release of destructive proteins and molecules. However, H. parasuis’s capsule interferes with the macrophage’s ability to mount this response. Therefore, the bacteria are able to live intracellularly in these immune cells. Once inside the macrophage, the bacteria prevent certain inflammatory messages from being produced as well as modify the surface proteins on the macrophage’s surface. This delays the host’s inflammatory response and gives the bacteria time to spread throughout the body. They can then enter the bloodstream and colonize elsewhere, such as the liver, brain and kidneys. In fact, H. parasuis itself is not what causes death when a pig is infected, it is rather the delayed-onset of systemic inflammation, which sometimes can lead to septic shock.

Overall, much is still unknown and not understood regarding H. parasuis. Further identification of virulence factors and their respective mechanisms will help elucidate aspects of its infection. Many aspects of its infection remain to be associated with and explained by identification of more virulence factors.

Figure 3: Bacterial infection process in the lung alveoli and consequent spreading throughout the body via the bloodstream. By G. Mezentzeff and V. Guay, 2019.

Prevention and Treatment

Good animal hygiene and nutrition as well as animal management are important factors that can help prevent incidence of infection. Most importantly, transport and the raising of animals need to be closely monitored to prevent the spread of disease to new regions and prevent outbreaks. Antibiotics, specifically prophylactic antimicrobials, can also be used as a method of prevention in piglets. This is useful since H. parasuis is able to colonize piglets as early as less than ten days of age. 

Another possible method used to control H. parasuis infection is vaccination, typically through the single dose injection of Parasail HPS injectable vaccine or Ingelvac HP-1 vaccine in the intramuscular space of the animal. Vaccines are administered to both piglets and mothers. The proportion of animals that are infected by H. parasuis is significantly lower in vaccinated than non vaccinated animals. Revaccination should take place right after the piglets stop drinking milk in order to provide the necessary protection against H. parasuis. Idealially, H. parasuis infection is prevented through the combination of vaccination of the sows and piglets and prophylactic antibiotic treatment of newborn piglets.

In the case where an animal is infected with H. parasuis, antibiotics can be used. For example, H. parasuis is successfully treated with synthetic penicillin, which acts to weaken and burst the cell walls of the bacteria. The drugs accomplish this by preventing the bacteria’s peptidoglycan, a cell wall layer, from crosslinking effectively during cell wall synthesis. Enroflox, Excede, and Draxxin, are all injectable over the counter antimicrobial solutions and three of the most effective treatments against H. parasuis. It is recommended to target antibiotic therapy towards the sows, as well as piglets, and to begin treatment immediately after symptoms are observed. The dose administered depends on the severity of the infection: if the disease has spread to the tissues, spinal fluids, or has affected joints, a higher dose is used. 

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Bacillus cereus


Bacillus cereus is a Gram-negative, spore-forming, rod-shaped bacterium (Figure 1) that causes food poisonings and food infections. This microorganism is a common soil inhabitant and can grow in almost all types of food. B. cereus was first identified as a foodborne pathogen by Hauge (1955) from a case of the diarrheal type of illness due to the consumption of vanilla extract. In 1971, the emetic type of food poisoning was found to be caused by B. cereus in fried rice, which gave its name of “fried rice syndrome”. The heat-resistant spore, a dormant structure of bacteria formed under stressful conditions, helps B. cereus to survive during food processing, thus raises issues of food safety, especially in pre-packed and ready-to-eat foods. 

Figure 1: Microscopic image of B. cereus stained with Gram’s method. Source: Dr. William A. Clark (1977), Public Health Image Library, Center for Disease Control. 


B. cereus forms resistant spores which protect it from extreme conditions such as temperature, pH, and radiation. The spore helps its persistence and transmission through processed, pasteurized, sterilized, and heat-treated food products, increasing its chance of human ingestion.  Contaminated foods either by B. cereus or the toxins produced by this bacterium food are the primary causes of the diseases (Figure 2). The food infection is caused by the growth of B. cereus in the intestine. Vegetables, meats, and dairy products are common vehicles for the transmission of this type of disease. Symptoms usually include abdominal pain and diarrhea that begin 4-16 hours after eating the contaminated food. On the other hand, the emetic syndrome of B. cereus food poisoning, also called “fried rice syndrome”, is due to the preformed toxin predominantly in starchy foods such as fried rice and pasta. Because the preformed toxins rather than the growth of the bacterium cause this type of illness, the onset of syndromes is more rapid compared to the diarrheal type. Symptoms are characterized by nausea and vomiting, starting in 1-5 hours after the consumption of contaminated foods. Both types of illnesses could be resolved without treatments and symptoms usually disappear within two days. However, individuals with compromised immune system may develop systemic infection due to introduction of the bacteria into the bloodstream.  



Figure 2: Transmission pathways of B. cereusdemonstrating how it enters the food production, followed by the human digestive system. The bacteria spread through insects, higher trophic animals like cows, or foods, and the ingestion of contaminated foods leads to illnesses. Source: Lina Bendjaballah 

Virulence Factors

B. cereus can form biofilms on abiotic surfaces or even living tissues. Biofilms are communities made up of bacteria and extracellular matrix, conferring B. cereus its adhesiveness and resistance to extreme temperature and pH. This bacterium secretes enormous number of metabolites, enzymes, toxins and generates resistant spores within biofilms. Ingestion of foods containing B. cereus in biofilms can lead to unproductive inflammation, a long-term inflammation that results in tissue death and connective tissue scarring. The biofilm helpB. cereus attach to the intestine tissuesallowing it to persistently trigger immune responses through the release of bacteria or toxins and enzymes it produces.  

B. cereus colonizes, grows and releases toxins in the human small intestine, which can cause food infections. Hemolysin BL (Hbl), non-hemolytic enterotoxin (Nhe), and cytotoxin K (CytK) are the three enterotoxins that B. cereus produces and are responsible for the diarrhoeal syndrome. These enterotoxins kill host cells by forming pores in their cell membranes (Figure 3). Hbl can also weaken immune responses by destroying the immune cells, such as macrophages and dendritic cells, which accelerates the spread of B. cereus and tissue damage. Widespread destruction of epithelial tissue in the intestine leads to ineffective absorption of water and, therefore, diarrhea.  

Figure 3: Illustration showing possible mechanism of Hbl toxin according to description of Shoeni and Wong (2005)As one of the three pore-forming enterotoxins, Hbl could perforate cell membrane through oligomerization (binding of smaller components into a unit) of its 3 components. This leads to massive ions and water loss of the targeted cell, severely disturbing the cell’s normal functions and eventually leading to cell lysis. Source: Xin Yue Liu 

On the other hand, the food poisoning or intoxication is attributed to the toxin called cereulide in the contaminated foods. This toxin is released in the food before it’s ingested. This preformed toxin is resistant to extreme pH, heat, and breakdown of proteins. Thus, cereulide in foods may persist after reheating and stomach acid. This emetic toxin causes mitochondria, the powerhouses of cells, to swell by interfering with the important energy production process called oxidative phosphorylation. This interference will halt energy production in the form of ATP, an organic chemical that provides the energy required in many biological functions such as muscle contraction, protein synthesis, regulation of normal cell functions, etc. In this case, the muscle cells of the gastrointestinal tract with dysfunctional mitochondria cannot survive due to energy deficiency, leading to cell death and inevitably causes damages in the muscle tissue. The progressive degeneration of the muscles leads to gastrointestinal dysmotility and symptoms like vomiting and nausea.

Other various enzymes also contribute to the virulence of B. cereus. Beta-lactamase provides the bacterium resistance to beta-lactam antibiotics such as penicillin and its derivatives. B. cereus also produces collagenase to degrade extracellular matrix (secreted proteins and polysaccharides providing structural and biochemical support to surrounding cells), thus facilitating its invasion of tissues. Protease is another weapon that B. cereus uses to infect host cells by hydrolyzing important proteins such as hemoglobin (carries oxygen in red blood cells) or albumin (regulates the osmotic pressure of the blood).  


The percentage of foodborne diseases due to B. cereus differs from country to country. During the 1990s, B. cereus was responsible for 47% of the total food poisoning cases in Iceland, 22% in Finland, and 8.5% in The Netherlands. This bacterium is also the primary cause of foodborne diseases in Norway. Other countries reported much lower numbers, such as England and Wales (0.7%), Japan (0.8%), USA (1.3%) and Canada (2.2%). Since most patients with food poisoning recover quickly and few seek medical advice, the number of B. cereus cases might be heavily underestimated. The dominant type of food poisoning caused by B. cereus also varies in different countries. The diarrheal syndrome is more prevalent in many European countries such as Hungary, Finland, Bulgaria, and Norway, whereas more cases of the emetic type have been reported in Japan. 

Foods contaminated by B. cereus or the toxins it produces are the major causes of foodborne illnessesAlthough B. cereus is an uncommon causative agent in the United States, an outbreak of B. cereus gastroenteritis occurred among 140 guests who attended a wedding reception in Napa County due to having contaminated Cornish game hens. Therefore, good hygiene and food handling practices are important in controlling B. cereus intoxication and food infection. 

Treatment and Prevention

Usually no treatment is needed in both the diarrheal and emetic cases since the symptoms are mild and can be resolved on its own. The patients can recover within two days. However, in some severe cases, administration of fluids is required to avoid excessive water loss. Since B. cereus is widely present in the environment, prevention methods thus focus on preventing the germination of spores and minimizing the production of toxins. Foods should be maintained above 60°C or below 4°C, and reheating premade food should ensure that the internal temperature reaches 74°C 


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Griffiths MW and Schraft H. (2017). Bacillus cereus Food Poisoning. Foodborne Diseases (third edition). 395-405. 

Kotiranta A, Lounatmaa K, Haapasalob M. (2000). Epidemiology and pathogenesis of Bacillus cereus infections. Microbes and Infections. 2(2): 189-198. 

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Bartonella quintana – Europe (WWI) 1914-1918

By Beatrice Cooney, Jasmine Coulombe & Leah Hiscott


Bartonella quintana infection, colloquially known as trench fever, is a vector-borne disease that is primarily transmitted by the human body louse. It was first described during World War I when it infected over 1 million soldiers in Europe. Upon its emergence, military medical officials were baffled by the symptoms arising in the soldiers – the characteristics of the condition were unlike anything they had seen before. Patients were suffering from severe headaches and dizziness; muscle pain and stiffness in the legs (particularly the shins); as well as relapsing fever. Doctors debated whether this was the emergence of a new disease or if it was an older one making a comeback, until it was officially recognized as a novel condition in the summer of 1916.

Trench fever is rarely fatal but it is extremely debilitating, which posed a significant efficiency problem for the armies affected by it. Infection is associated with a variety of clinical conditions such as chronic bacteremia, the presence of bacteria in the bloodstream; endocarditis, an infection of the lining of the heart; lymphadenopathy, a disease of the lymph nodes; and bacillary angiomatosis, which causes lesions on the surfaces of many different organs. Trench fever is thus a gateway to much more serious health concerns.

B. quintana has not since caused an epidemic to the scale of WWI, but it is not eradicated either. Since the 1990’s, B. quintana has reemerged as “urban trench fever” among impoverished and homeless populations that are subjected to unsanitary and crowded conditions that lend itself to the parasites that could transmit the infection. 

B. quintana is a facultative, intracellular, Gram-negative rod with the human body louse, Pediculus humanus corporis, typically acting as its vector. The lice primarily infest clothing and the unhygienic and crowded conditions of the trenches during the war aided in its proliferation. B. quintana multiples in the intestines of the louse and is passed on to humans via the spreading of its feces on damaged skin. The lice also bite their victims, injecting an anesthetic that prompts an allergic reaction that leads to scratching, which only further facilitates B. quintana’s transmission.

Fig.1: Dorsal view of a female body louse, Pediculus humanus var. corporis. Some of the external morphologic features displayed by members of the genus Pediculus include an elongated abdominal region without any processes, and three pairs of legs, which are all equal in length and width. Source: CDC Public Health Image Library.

Fig 2: Example of lesions caused by scratching, allowing a route of transmission for the bacteria to humans through the louse feces in the abrasions. Source: Foucault, C., Brouqui, P., & Raoult, D. (2006). Bartonella quintana Characteristics and Clinical Management. Emerging Infectious Diseases, 12(2), 217-223.

Source & cause of the outbreak

With its first appearance during WWI, trench fever was thought to be some type of infection and was typically compared to malaria due to the omnipresence of fever, a cardinal sign of infection. Thanks to careful observation of cases coming into the infirmary, it was correctly postulated that the condition might be carried by a parasite found in the trenches. Physicians named voles or mice as the vector, shedding light on the horrendous conditions in the trenches until body louse was dubbed the culprit of the disease. This was supported by the fact that the disease was especially prevalent in the winter, when flies and mosquitos were absent from the trenches. By the end of 1916, most had agreed that louse transmitted B. quintana, as this was the most common parasite found in the trenches. However, the definitive experimental proof was still lacking. By 1917, two years after its first appearance, both the British and the Americans set up committees dedicated to tracking down the transmissive agent of the disease. The Americans concluded that it was the bite of the louse that transmitted the disease, making it the vector. However, it was the British that demonstrated that it was the transmission of louse excreta into the damaged skin that conveyed the causative agent. It is now known that mature louse can live for up to 30 days.

The infection itself is sudden, persistent and unpleasant. At the time of infection, it is common to experience a fever lasting between 2 to 6 days, accompanied by headaches, back and leg pain, and a fleeting rash. Recovery can take up to two months and relapse, even 15 years later, is common; about five percent of cases become chronic. The bacteria carried by the lice infect the blood, bone marrow, and skin of its patients and can be detected even after treatment and recovery. Today, the disease is treated with antibiotics, typically chlortetracycline, but others options are available as well. 

Ending the outbreak

Despite the slow response to the outbreak containment, treatment ended up being extremely successful. Even before the real causative agent was discovered, trench fever was recognized as a serious issue likely arising from the abhorrent conditions endured by soldiers. After identification, the “Department of Government Circular Memorandum No. 16” was outlined as a reference for better health. Although many of the suggestions were unrealistic for those on the front lines, serious effort was made nonetheless. Regular showers every other week were demanded, and mobile delousing stations moved around base camps in an effort to eradicate the source. The most effective effort, however, came at the end of the war. For fear that the disease might spread to Britain’s general population, strict sanitation regimes were implemented for all soldiers returning home. Thankfully, this was successful and the British population was able to avoid the disease many of their soldiers were due to suffer from for the rest of their days.


Research continued into the root cause of trench fever, despite the fact it was not prevalent in the general population after the outbreak during the war, it did reappear as a small epidemic in the German troops on the Eastern front during World War II. Furthermore, it still appears today in homeless and immunocompromised populations. As B. quintana was not cultured during the outbreak in the first World War, work slowly continued to try and isolate the bacterium causing trench fever. While the disease was putatively linked to louse infestation, the bacterium itself was not isolated until 1961 by J William Vinson of Harvard University and Henry Fuller of Walter Reed Army Institute of Research. As this occurred after WWII, the defensive strategies for the second war focused on preventing louse infestation by providing better hygiene for soldiers, as well as soldiers tended to be more spread out and mobile. After the second World War, antibiotic susceptibility testing and genome sequencing occurred and therefore lead to a better understanding of the transmission of the disease and its treatment.


The outbreak of trench fever posed a significant hurdle for armies during WWI, leading to a loss in soldiers and an increased demand for medical care. The slow response to determine the cause of the disease, due to the lack of knowledge at the time regarding the classification of bacteria, was detrimental to the war effort. However, as the war ended, the disease was well contained and extreme preventative measures halted the spread to the general public. While trench fever is still seen today in niche populations, general understanding, prevention, and treatment of the disease has greatly increased, alleviating the threat of future outbreaks.


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