The long range objective of the proposed study is to gain insight into the pathogenetic mechanisms of Bartonella species during opportunistic infection of patients co-infected with HIV. Bartonella syndromes in HIV-infected patients include severe, even fatal infections such as bacillary angiomatosis, peliosis hepatitis, relapsing bacteremia, endocarditis, cat scratch disease, neuroretinitis and encephalopathy. From clinical observations, there are two striking manifestations of Bartonella pathogenesis: relapsing and persistent bloodstream infections and vascular proliferative lesions, yet nothing is known about the bacterial pathogenetic mechanisms involved in either, largely because no animal models exist. the immediate objective of these studies is to study the mechanisms of Bartonella pathogenesis by developing an animal model, and utilizing this animal model to characterize the host response to infection and mechanisms of virulence gene expression associated with B. henselae and B. quintana. The applicant's first goal is to develop an animal model for AIDS-associated opportunistic Bartonella infections in by infecting animals with B. henselae or B. quintana, with the goal of inducing one or both endpoint disease manifestations: persistent bloodstream infection and angiogenic lesions. The second goal is to utilize the model to study Bartonella pathogenesis (course of infection, pathological changes, humoral immune response). Through development of an animal model and subsequent study of the disease course, pathological manifestations and mammalian host-bacterium interactions, the applicants hope to gain insight into the basis for Bartonella pathogenesis including host immune response and persistent and relapsing infection, which will ultimately lead to improved diagnosis, treatment and prevention of Bartonella infection in HIV-infected patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI043703-04
Application #
6475509
Study Section
Special Emphasis Panel (ZRG5-AARR-4 (01))
Program Officer
Lambros, Chris
Project Start
1998-12-01
Project End
2004-11-30
Budget Start
2001-12-01
Budget End
2004-11-30
Support Year
4
Fiscal Year
2002
Total Cost
$323,063
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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Chomel, Bruno B; Henn, Jennifer B; Kasten, Rickie W et al. (2009) Dogs are more permissive than cats or guinea pigs to experimental infection with a human isolate of Bartonella rochalimae. Vet Res 40:27
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Eremeeva, Marina E; Gerns, Helen L; Lydy, Shari L et al. (2007) Bacteremia, fever, and splenomegaly caused by a newly recognized bartonella species. N Engl J Med 356:2381-7
Zhang, Peng; Chomel, Bruno B; Schau, Maureen K et al. (2004) A family of variably expressed outer-membrane proteins (Vomp) mediates adhesion and autoaggregation in Bartonella quintana. Proc Natl Acad Sci U S A 101:13630-5
Rolain, J M; Brouqui, P; Koehler, J E et al. (2004) Recommendations for treatment of human infections caused by Bartonella species. Antimicrob Agents Chemother 48:1921-33
Koehler, Jane E; Sanchez, Melissa A; Tye, Sherilyn et al. (2003) Prevalence of Bartonella infection among human immunodeficiency virus-infected patients with fever. Clin Infect Dis 37:559-66
Yamamoto, Kazuhiro; Chomel, Bruno B; Kasten, Rickie W et al. (2003) Infection and re-infection of domestic cats with various Bartonella species or types: B. henselae type I is protective against heterologous challenge with B. henselae type II. Vet Microbiol 92:73-86
Chang, Chao-Chin; Chomel, Bruno B; Kasten, Rickie W et al. (2002) Molecular epidemiology of Bartonella henselae infection in human immunodeficiency virus-infected patients and their cat contacts, using pulsed-field gel electrophoresis and genotyping. J Infect Dis 186:1733-9

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