by Adriana Kalaska and Jessica Garofalo

Introduction     

Pasteurella multocida is the most common cause of a disease known as Pasteurellosis. This disease is zoonotic as it infects humans through an animal vector. P. multocida is found in the normal oral and nasal bacterial communities of many species. The bacteria is named after Louis Pasteur who first isolated the stain in 1880 from birds suffering from cholera.  

Disease

Pasteurellosis is transmitted to humans by cat or dog bites and licks via a wound in the skin. Symptoms of skin infection usually appear after 24-48 hours. However, people with weak immune systems cannot clear this initial infection effectively. This allows P. multocida to spread to the blood and sometimes to the brain, causing swelling, fever, blood poisoning, and even death. In animals, colonies of P. multocida can also become invasive and spread to the lungs under stressful conditions when the host immune system is weakened. This opportunistic pathogen is able to overwhelm the host defenses. Phagocytes, cells that normally ingest and destroy the bacteria, cannot kill P. multocida efficiently due to the bacteria’s protective capsule, which is what leads to the progression of respiratory diseases. If an animal has a heavy bacterial burden, airborne transmission of the pathogen to others in the herd is possible (see Figure 1). In rare cases, P. multocida infection can also cause severe inflammation, that can lead to cellular damage.

Figure 1:  Different transmission pathways of P. multocida. Left: The evolution of commensal P. multocida into upper respiratory tract infections in farm animals when faced with stressors such as dramatic temperature changes and lack of or improper nutrition. Right: Transmission of P. multocida found in the oral and nasal cavities in common household pets to humans. Created by Garofalo & Kalaska, images sourced from: https://openclipart.org.

Epidemiology

Roughly 300 000 annual visits to emergency rooms in the U.S. are due to animal bites or scratch wounds. Respectively, 50% and 75% of dog and cat bites result in soft tissue infections caused by pasteurella species in humans, as these are the most common carrier animals. The very young (underdeveloped defenses), the elderly (tired defenses), and individuals with underlying conditions (diabetes, chronic diseases) are more susceptible to proliferative infection. Additionally, anyone who frequently handles animals without handwashing is at greater risk of contraction. Overall, death in humans due to P. multocida is extremely rare.

Pasteurellosis also affects domesticated animals such as cattle, buffalo, sheep, goats, horses, pigs, poultry, rabbits, and rats. Some manifestations of this bacteria in these species are: fowl cholera, hemorrhagic septicemia, pneumonia, respiratory atrophic rhinitis, and purulent rhinitis. These infections cause high mortality rates reaching up to 50% in animals with clinical disease. In particular, it causes 30% of total cattle deaths worldwide. Consequently, pasteurellosis causes substantial economic deficits. It is estimated to result in losses of $1 billion in the North American beef industry alone.

Virulence Factors

The main factor that allows P. multocida to infect and spread within hosts is the bacterial capsule that is made up of complex carbohydrate combinations. The capsule masks specific surface molecules of the bacteria, called antigens, that are recognized by the host’s immune system. Furthermore, variability of this structure makes it hard for the immune system to target the bacterial cells, as any memory produced by special immune cells to one form of the capsule will not be specific for new versions. Immune system memory is mediated by  T cells and B cells, which respond to specific antigen. T cells activate B cells which then produce antibodies. Antibodies bind and surround bacteria and bring them to other immune cells to be degraded, which is an important process known as opsonization.

The capsule of most bacterial species protects them from the natural defenses of the skin such as antimicrobial peptides, which are small molecules that form pores or bipass the bacterial membrane to kill the pathogen. Without a capsule, P. multocida is also sensitive to proteins of the blood, called the complement. These tag the cell and attract other complement proteins or antibodies to attach, creating a pore in the membrane. They may also attract macrophages which perform phagocytosis: the engulfing and destruction of bacterial cells using toxic chemicals that are found in a separate compartment called the phagosome.

Thus, this capsule allows the bacteria to spread and invade tissues without being detected by the host (See Figure 2). Additionally, it is believed that the bacterial capsule is also capable of mimicking the host. This means that the components making up the layer surrounding the membrane of the bacteria resemble components of the host cells. P. multocida uses this as another method to evade phagocytes, as the host immune cells are programmed not to recognize and target proteins that resemble themselves.

Figure 2: The function of the capsule. A mutant bacteria without the capsule is easily detected and destroyed by the macrophage phagosome. Encapsulated bacteria mimicking the host are protected from detection and proliferate. Created by Garofalo & Kalaska.

The capsule of P. multocida exists as 5 different types called A, B, C, D, and E. The type of capsule determines the species of animal that the bacteria infects as well as the specific disease that it causes. Furthermore, the thickness of all capsules depends on the level of some nutrients, such as iron, that the bacteria has available to it. Finally, some research has revealed that capsules may play a role in the adhesion of P. multocida to the host cells, facilitating attachment and allowing the bacteria to remain inside of tissues and reproduce.

Treatment

In humans, animal bite infections are treated with broad range antibiotics. This is done to target multiple bacterial species that have the ability to survive in the low oxygen environment of a deep wound. Pasteurella species are susceptible to penicillin, but the preferred treatment is a mixture of amoxicillin/clavulanate or ampicillin/sulbactam to attack the combination of bacteria in bite wounds. These antibiotics target cell wall synthesis which is necessary for bacterial growth and division.

In domesticated animals, treatment with antibiotics is expensive and shown to be inefficient. Research into vaccines has produced a semi-efficient live attenuated vaccine, containing a mutated strain of P. multocida that lacks multiple genes required for infection. This allows the host to produce memory cells against this pathogen and upon future infections they will produce a rapid targeted response to clear it. Unfortunately, these vaccines have resulted in some systemic infections leading to death of vaccinated animals.

References

Ahmad, T. A., et al. (2014). Development of immunization trials against Pasteurella
multocida. Vaccine, 32, 909–917.

Giordano, A., et al. (2015). Clinical Features and Outcomes of Pasteurella multocida Infection. Medicine 94, 1-7.

Harper, M., and Boyce, J.B. (2017). The Myriad Properties of Pasteurella
multocida Lipopolysaccharide. Toxins 9, 254.

Marcantonio, Y. C., et al. (2017). Disseminated Pasteurella multocida infection:
Cellulitis, osteomyelitis, and myositis. IDCases 10, 68–70.