Clostridium perfringens

by Vittoria Lipari and Andréanne Breton-Carbonneau

Introduction

Clostridium perfringens is the 3rd most common form of food poisoning, causing 1 million cases of food poisoning per year. It can occasionally lead to lethal inflammation and necrotic enteritis (death of the intestinal tissue). In addition, C. perfringens induces the fatal disease gas gangrene, which causes myonecrosis (death of muscle tissue). This bacteria was recognized in 1898 and was the primary lethal pathogenic agent from wounds in World War I. C. perfringens is an anaerobic bacteria, meaning it grows in the absence of oxygen. This bacteria can normally live in the human intestine and will decay vegetation when in the environment. C. perfringens can thus be found commensally (without bodily harm) in the human intestinal tract, in sewage, and in soil, however it can also cause serious diseases.

Figure 1: An image of Clostridium perfringens under the microscope. They are rod-shaped and stain purple under the gram stain, indicating that this bacteria is Gram positive (has a peptidoglycan layer not surrounded by an outer membrane) . Source: Centers for Disease Control and Prevention 2015.

Figure 1: An image of Clostridium perfringens under the microscope. They are rod-shaped and stain purple under the gram stain, indicating that this bacteria is Gram positive (has a peptidoglycan layer not surrounded by an outer membrane) . Source: Centers for Disease Control and Prevention 2015.

Disease

Soil-borne pathogens like C. perfringens often colonize low nutrient environments. When a person accidentally eats this bacterium, C. perfringens enters a high-nutrient environment and reproduce quickly. They form spores, a protected and resistant form of the bacteria, that spread rapidly through the circulation. These spores reach tissues of the intestine and muscle, where they further replicate. The rapid multiplication causes tissue damage resulting in necrotic (dead cell) lesions, although the majority of tissue damage and cell death comes from the toxins the bacteria secrete. Symptoms of food poisoning manifest 8-18h after infection and include abdominal cramping, nausea, and diarrhea. This gastrointestinal infection can sometimes evolve into Pidbel, the rare form of clostridial necrotic enteritis, if the infective strain produces the right toxin. Signs of Pigbel disease include vomiting, bloody stool, abdominal pain, and occasionally toxemia (blood poisoning with toxins).

Another way C. perfringens can cause disease is when it enters deep, already existing wounds and mostly infects the surrounding muscle. C. perfringens is capable of anaerobic fermentation within the muscle tissue, a process that produces carbon dioxide (CO2) gas and results in further death of the tissue. Infection can be established in as little as 6-8 hours and death of the host can result within 24-48 hours. Gas gangrene can be easily identified by cell necrosis at the wound site, pain and swelling, fever, and a foul-smelling discharge (Figure 2).

Figure 2: Image of patient with gas gangrene exhibiting swelling and necrotic blisters, or bullae, caused by the CO2 production within the muscles. Source: Schröpfer et. al. 2008.

Figure 2: Image of patient with gas gangrene exhibiting swelling and necrotic blisters, or bullae, caused by the CO2 production within the muscles. Source: Schröpfer et. al. 2008.

Epidemiology

People in areas with poor nutrition and food hygiene, such as New Guinea, are more susceptible to the evolved form of C. perfringens food poisoning: clostridial necrotizing enteritis. Contaminated foods, such as meats and gravies, are common causes of C. perfringens food poisoning. Large quantities of food that remain warm over long periods of time are at the highest risk of causing illness, thus hospitals, schools, and prison cafeterias are typical areas of C. perfringens food poisoning outbreaks.

C. perfringens infection resulting in gas gangrene represents 10%-12% of wound deaths during World War I. With improved battlefield surgical practices, the mortality rate of this disease in the Vietnam War decreased to 0.016%. Gas gangrene results from unhygienic surgical practices and suturing contaminated wounds before elimination of the bacteria, which is why it is commonly associated as a military disease.

Individuals with pre-existing conditions that obstruct blood flow, such as diabetes and atherosclerosis, are the most susceptible to gas gangrene. C. perfringens infection is also associated with multiple sclerosis (MS), however, the interactions between the bacteria and the disease are currently not well understood.

Virulence systems

C. perfringens produces a wide variety of toxins that do harm to the body. The different strains of this species are organised into 5 serotypes (groups) based on which toxins they produce. The commensal type of C. perfringens that reside in human intestines is called type A. Only 1-5% of all type A strains can produce the toxin that causes food poisoning. When the bacteria form spores in the small intestine, they start to release this toxin. In cases where the victim cannot produce diarrhea to eliminate some of the toxin, it will move into the blood to get to other tissues and cause organ damage, eventually leading to heart failure and death. Type C strains produce a different toxin that is responsible for Pigbel disease. Both toxins produced by type A and C strains form a hole in the host cell membrane, causing cell death.

Type A strains also produce the toxins responsible for gas gangrene. One of these toxins tells the host cell to call white blood cells to the blood vessels instead of the site of infection. This inhibits white blood cells from reaching the bacterial cells, thus preventing the body from fighting the infection. The other toxin produced by Type A strains creates a pore in the host cell membrane, causing the host cell to lyse (rupture). Without either one of these two toxins, C. perfringens cannot cause gas gangrene.

Treatment

Antibiotics cannot be used as treatment for C. perfringens intestinal infections because they will kill other bacteria that normally live in the host. If the good bacteria of your intestines are gone, C. perfringens has no competition for nutrients and will grow quickly and cause disease. Successful treatment of this pathogen requires rehydration of the patient and rest so that the body’s immune system can fight the bacteria on its own.

For infections originating from a deep wound, the area must be cleaned as best as possible and antibiotics should be used. Penicillin or a clindamycin/metronidazole combination are good choices. Patients must be under intensive care as organ failure is common with gas gangrene. In some studies, scientists were able to isolate one of the toxins produced by Type A C. perfringens and use it as a vaccine in mice, however further research needs to be done to develop a safer vaccine for humans.

References

Centers for Disease Control and Prevention. Clostridium perfringens. 2015.

Lentino JR. Clostridial Necrotizing Enteritis. 2013. Merck Manual of Diagnosis and Therapy.

Nagahama M, Ochi S, Oda M, Miyamoto K, Takehara M, Kobayashi K. Recent Insights into Clostridium perfringens Beta-Toxin. 2015. Toxins (Basel). 7(2):396–406.

Oda M, Shiihara R, Ohmae Y, Kabura M, Takagishi T, Kobayashi K, Nagahama M, Inoue M, Abe T, Setsu K, Sakurai J. Clostridium perfringens alpha-toxin induces the release of IL-8 through a dual pathway via TrkA in A549 cells. 2012. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease. 1822(10):1581-1589.

Pailler JL, Labeeu F. Gas gangrene: a military disease? 1986. Acta Chir Belg. 86(2):63-71.

Schröpfer E, Rauthe S, Meyer T. Diagnosis and misdiagnosis of necrotizing soft tissue infections: three case reports. 2008. Cases J. 1(1): 252.

Stevens DL and Bryant AE. The Role of Clostridial Toxins in the Pathogenesis of Gas Gangrene. 2002. Clinical Infectious Diseases. 35(1): 593-600.

United States Food and Drug Administration. Clostridium perfringens in foods. 1982. Washington, D.C. : Dept. of Health and Human Services, Food and Drug Administration.

Uzal FA, Freedman JC, Shrestha A, Theoret JR, Garcia J, Awad MM, Adams V, Moore RJ, Rood JI, McClane BA. Towards an understanding of the role of Clostridium perfringens toxins in human and animal disease. 2014. Future Microbiol. 9(3): 361–377.

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