Francisella tularensis is the causative agent of tularemia, an acute febrile infection with variable presentation and outcomes. Although the agent is said to be maintained in nature by cycles involving ticks and rodents or rabbits, its great infectivity and presumptiveenvironmental stability suggestsother modes of perpetuation. Our longterm goal is to determine the proximal determinants of risk for outbreaksof tularemia, and in particular,how the agent is maintained between epizootics. The specific hypothesis is that multiple modes of transmission are facilitated by a metapopulation structure of genetic variants within an enzootic focus; certain variants may be better adaptedto ticks as opposed to environmental reservoirs. We base our hypothesis on our investigationof the ongoing pneumonic tularemia outbreak on Martha's Vineyard, wherein we have found (1) that 11 F. tularensis variants circulate in our island study sites; and (2) that certain of these variants appear to be associated solely with ticks or with animals. Based on these observations, we now seek to determine experimentallywhether certain variants are more likely to be inherited by ticks, remain stable within the environment, or cause pulmonary pathology.
The specific aims, therefore, are to: 1. Determine whether variants differ in their capacity to be transmitted by ticks, including maintenance by inheritance. We will clone strains from the multiple loci variable number tandem repeat analysis (MLVA)-defined genotypes, and measure the vector competence of various ticks for such clones. 2. Determine whether variants differ in their capacity to stably persist in the environment, including resistance to dessication, survival in water, and colonisation of freeliving or parasitic cyst-forming protozoa. We will measure the viability and survival of each genotype under simulated environmental stresses in vitro. 3. Determine whether variants differ in their infectivity to and virulence within rodents, including capacity to induce pulmonary pathology or hematogenously disseminate. Rats and mice will be infected by intratracheal instillation, as well as parenteral delivery, and tissues examined by histopathology,immunohistochemistry, PCR, cultivation, and cytokine mRNA expression. Taken together, these observations will provide a basis for understanding how the agent of tularemia is perpetuated on Martha's Vineyard, and why pneumonic human disease is prevalent there.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI064218-03
Application #
7350858
Study Section
Special Emphasis Panel (ZRG1-VB (01))
Program Officer
Mukhopadhyay, Suman
Project Start
2006-02-01
Project End
2011-01-31
Budget Start
2008-02-01
Budget End
2009-01-31
Support Year
3
Fiscal Year
2008
Total Cost
$374,234
Indirect Cost
Name
Tufts University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
039318308
City
Boston
State
MA
Country
United States
Zip Code
02111
Goethert, Heidi K; Telford 3rd, Sam R (2014) Not ""out of Nantucket"": Babesia microti in southern New England comprises at least two major populations. Parasit Vectors 7:546
Goethert, Heidi K; Telford 3rd, Sam R (2011) Differential mortality of dog tick vectors due to infection by diverse Francisella tularensis tularensis genotypes. Vector Borne Zoonotic Dis 11:1263-8
Berrada, Zenda Lea; Telford Iii, Sam R (2011) Survival of Francisella tularensis Type A in brackish-water. Arch Microbiol 193:223-6
Berrada, Zenda L; Goethert, Heidi K; Cunningham, Jenny et al. (2011) Rickettsia rickettsii (Rickettsiales: Rickettsiaceae) in Amblyomma americanum (Acari: Ixodidae) from Kansas. J Med Entomol 48:461-7
Navarro, Paula; Garcia-Moliner, Maria L; McMahon, James H et al. (2011) Histologic, immunohistochemical, microbiological, molecular biological and ultrastructural characterization of pulmonary tularemia. Pathol Res Pract 207:63-6
Telford 3rd, Sam R; Goethert, Heidi K (2010) Toward an understanding of the perpetuation of the agent of tularemia. Front Microbiol 1:150
Berrada, Zenda L; Telford 3rd, Sam R (2010) Diversity of Francisella species in environmental samples from Martha's Vineyard, Massachusetts. Microb Ecol 59:277-83
Telford 3rd, Sam R; Wormser, Gary P (2010) Bartonella spp. transmission by ticks not established. Emerg Infect Dis 16:379-84
Matsumoto, Kotaro; Cook, Joseph A; Goethert, Heidi K et al. (2010) Bartonella sp. Infection of voles trapped from an interior Alaskan site where ticks are absent. J Wildl Dis 46:173-8
Goethert, Heidi K; Telford 3rd, Sam R (2010) Quantum of infection of Francisella tularensis tularensis in host-seeking Dermacentor variabilis. Ticks Tick Borne Dis 1:66-8

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