Nicholas Friedeman

Nicholas Friedeman

Mar 24, 2025

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Lab Note 3: Introduction to the Pathogens

Of the known disease threats to muskrats, bacteria represent one of the more studied and recorded groups (Ganoe et al. 2020). We are focusing our study on two bacteria, Francisella tularensis and Clostridium piliforme, because of their significance to muskrats in past literature over the last century relative to other infectious agents.   Francisella tularensis is gram-negative bacteria and is the causative agent of the disease referred to as tularemia. Francisella tularensis is a zoonotic pathogen meaning it can cause disease in both humans and animals. It is very transmissible and can be spread through most major transmission pathways (vector borne, ingestion, inhalation, or direct contact with contaminated objects, food, water, etc.) In fact, it is so infectious that it is classified as a category A bioterrorism agent by the National Institute of Health https://www.ncbi.nlm.nih.gov/books/NBK22924/.  

Image of F. tularensis under a microscope. The pink color when exposed to a gram stain is why they are referred to as gram-negative.

Francisella tularensis is typically maintained and amplified across the landscape within rodents and lagomorphs (rabbits) and to some capacity in arthropod vectors like ticks (Kugeler et al. 2009) (Telford and Goethert 2020) (Mani et al. 2015). They are referred to as reservoir/amplification hosts because they help the pathogen exist and spread. Although rodents can act as reservoirs, they are also susceptible and can succumb to infection with F. tularensis depending on the host species infected. Tularemia has been reported in muskrats over the course of the last century and is known to have occurred as epizootics, temporary but widespread disease in population, in muskrats of Canada and the US (Ganoe et al. 2020).  

Histologic image of C. piliforme in the liver tissue of a horse. The red squares indicate the clumps of bacteria within the tissues. Image taken by the Oklahoma Stat University Center for Veterinary Health Sciences.

Clostridium piliforme is another gram-negative bacterial pathogen that displays the capacity to infect a wide array of animals from rodents and ruminants to non-human primates and even birds (Garcia et al. 2022) (Brooks et al. 2006) (Ikegami et al. 1999) (Neto et al. 2015) (Raymond et al. 2001) (Sasseville et al. 2007). Infection has also been documented in one human who was co-infected with HIV-1 (Smith et al. 1996). In such cases where C. piliforme infection develops into disease, it is referred to as Tyzzer’s disease. Muskrats of North America have had well documented epizootic outbreaks of Tyzzer's disease (Ganoe et al. 2020). Like other bacteria in the genus Clostridium, C. piliforme can produce spores during non-favorable environmental conditions, prolonging their stability in the environment and increasing the odds a host may encounter viable bacteria. It is that environmental stability that fuels the prevailing theory of transmission, where the hosts uptake bacterial spores primarily via ingestion. Once in the host, the bacteria colonize the gastrointestinal tract and can enter circulation in more severe cases.  

References
  • 1. Smith, K. J., Skelton, H. G., Hilyard, E. J., Hadfield, C. T., Moeller, R. S., Tuur, S., ... & Angritt, P. (1996). Bacillus piliformis infection (Tyzzer's disease) in a patient infected with HIV-1: confirmation with 16S ribosomal RNA sequence analysis. Journal of the American Academy of Dermatology, 34(2), 343-348.
  • 2. Sasseville, V. G., Simon, M. A., Chalifoux, L. V., Lin, K. C., & Mansfield, K. G. (2007). Naturally occurring Tyzzer's disease in cotton-top tamarins (Saguinus oedipus). Comparative medicine, 57(1), 125-127.
  • 3. Raymond, J. T., Topham, K., Shirota, K., Ikeda, T., & Garner, M. M. (2001). Tyzzer's disease in a neonatal rainbow lorikeet (Trichoglossus haematodus). Veterinary Pathology, 38(3), 326-327.
  • 4. Neto, R. T., Uzal, F. A., Hodzic, E., Persiani, M., Jolissaint, S., Alcaraz, A., & Carvallo, F. R. (2015). Coinfection with Clostridium piliforme and Felid herpesvirus 1 in a kitten. Journal of Veterinary Diagnostic Investigation, 27(4), 547-551.
  • 5. Ikegami, T., Shirota, K., Une, Y., Nomura, Y., Wada, Y., Goto, K., ... & Fujiwara, K. (1999). Naturally occurring Tyzzer's disease in a calf. Veterinary pathology, 36(3), 253-255.
  • 6. Brooks, J. W., Whary, M. T., Hattel, A. L., Shaw, D. P., Ge, Z., Fox, J. G., & Poppenga, R. H. (2006). Clostridium piliforme infection in two farm-raised white-tailed deer fawns (Odocoileus virginianus) and association with copper toxicosis. Veterinary Pathology, 43(5), 765-768.
  • 7. García, J. A., Navarro, M. A., Fresneda, K., & Uzal, F. A. (2022). Clostridium piliforme infection (Tyzzer disease) in horses: retrospective study of 25 cases and literature review. Journal of Veterinary Diagnostic Investigation, 34(3), 421-428.
  • 8. Mani, R. J., Metcalf, J. A., & Clinkenbeard, K. D. (2015). Amblyomma americanum as a bridging vector for human infection with Francisella tularensis. PLoS One, 10(6), e0130513.
  • 9. Telford III, S. R., & Goethert, H. K. (2020). Ecology of Francisella tularensis. Annual review of entomology, 65(1), 351-372.
  • 10. Kügeler, C., Meier, M., Rosezin, R., Gilles, S., & Waser, R. (2009). High density 3D memory architecture based on the resistive switching effect. Solid-state electronics, 53(12), 1287-1292.
  • 11. Ganoe LS, Brown JD, Yabsley MJ, Lovallo MJ, Walter WD. A review of pathogens, diseases, and contaminants of muskrats (Ondatra zibethicus) in North America. Frontiers in Veterinary Science. 2020;7:233.
  • 12. Ganoe LS, Brown JD, Yabsley MJ, Lovallo MJ, Walter WD. A review of pathogens, diseases, and contaminants of muskrats (Ondatra zibethicus) in North America. Frontiers in Veterinary Science. 2020;7:233.
  • 13. Ganoe LS, Brown JD, Yabsley MJ, Lovallo MJ, Walter WD. A review of pathogens, diseases, and contaminants of muskrats (Ondatra zibethicus) in North America. Frontiers in Veterinary Science. 2020;7:233.

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About This Project

The muskrat, a charismatic semi-aquatic rodent, has experienced long-term declines across the United States dating back to the 1970s. The factors for this decline remain unclear. Our research will investigate health challenges in eastern US muskrat populations by determining the prevalence and distribution of pathogens and contaminants in these declining animals. The outcomes from our effort can provide context to observed declines and serve as a guide for management efforts of the species.

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