The long range objective of the proposed study is to gain insight into the pathogenic mechanisms of Bartonella, an opportunistic pathogen of AIDS patients. B. quintana is a fastidious, gram-negative bacterium that causes bacillary angiomatosis, a vascular proliferative lesion affecting HIV-infected patients. Relapsing and/or persistent bloodstream infection is a frequent manifestation of B. quintana infection that occurs in patients at all stages of HIV infection and can last for months in humans, causing debilitating and even fatal sequelae. We identified a gene family encoding outer membrane proteins (OMP) of Bartonella that are variably expressed over time, and that undergo rearrangement and/or deletion of one or more of the tandemly-arranged, paralogous genes during prolonged blood stream infection. Members of this variably-expressed outer membrane protein (Vomp) family are orthologs of several well-studied OMP adhesins in other gram-negative bacteria, including the YadA of Yersinia. The Vomp are members of the trimeric autotransporter adhesin (TAA) family of virulence determinants, and the Vomp represent a multifunctional protein involved in Bartonella pathogenesis in humans. The virulence properties of the Vomp that we have identified include phase variation, autoaggregation, hemagglutination and binding to host cells. The immediate objective of this proposal is to study the mechanisms of Bartonella pathogenesis by elucidating the virulence properties of the B. quintana Vomp including characterization of the: 1. Molecular architecture and mechanism of autotransport by the B. quintana Vomp TAA; 2. Interaction of surface-expressed Vomp adhesins with endothelial cells (EC) in vitro; and 3. Role of the individual Vomp in determining binding specificity of B. quintana to host cells (RBC, EC) and host cell components (extracellular matrix, collagens). In summary, the 100 kDa TAA members of the Vomp family are multifunctional virulence determinants that mediate pathogenesis in the human host. The ultimate goal of this project is to characterize at the molecular, bacterial and host cellular levels, the contribution of the Vomp family and the individual Vomp adhesins to Bartonella-mediated pathogenesis in the HIV-infected human. 7.
Bartonella is a bacterium that causes severe illness in patients with a weakened immune system, including those with AIDS, cancer and transplanted organs. We are investigating how this bacterium is able to cause long-term infections in the blood of humans, sometimes for years, so that infection can be prevented. ? ? ?
|Kim, J H; Previte, D J; Yoon, K S et al. (2017) Comparison of the proliferation and excretion of Bartonella quintana between body and head lice following oral challenge. Insect Mol Biol 26:266-276|
|Lee, Sulggi A; Plett, Sara K; Luetkemeyer, Anne F et al. (2015) Bartonella quintana Aortitis in a Man with AIDS, Diagnosed by Needle Biopsy and 16S rRNA Gene Amplification. J Clin Microbiol 53:2773-6|
|Previte, D; Olds, B P; Yoon, K et al. (2014) Differential gene expression in laboratory strains of human head and body lice when challenged with Bartonella quintana, a pathogenic bacterium. Insect Mol Biol 23:244-54|
|Abromaitis, Stephanie; Nelson, Christopher S; Previte, Domenic et al. (2013) Bartonella quintana deploys host and vector temperature-specific transcriptomes. PLoS One 8:e58773|
|Abromaitis, Stephanie; Koehler, Jane E (2013) The Bartonella quintana extracytoplasmic function sigma factor RpoE has a role in bacterial adaptation to the arthropod vector environment. J Bacteriol 195:2662-74|
|Roden, Julie A; Wells, Derek H; Chomel, Bruno B et al. (2012) Hemin binding protein C is found in outer membrane vesicles and protects Bartonella henselae against toxic concentrations of hemin. Infect Immun 80:929-42|
|Vigil, Adam; Ortega, Rocio; Jain, Aarti et al. (2010) Identification of the feline humoral immune response to Bartonella henselae infection by protein microarray. PLoS One 5:e11447|
|Henn, Jennifer B; Gabriel, Mourad W; Kasten, Rickie W et al. (2009) Infective endocarditis in a dog and the phylogenetic relationship of the associated ""Bartonella rochalimae"" strain with isolates from dogs, gray foxes, and a human. J Clin Microbiol 47:787-90|
|Bouchouicha, Rim; Durand, Benoit; Monteil, Martine et al. (2009) Molecular epidemiology of feline and human Bartonella henselae isolates. Emerg Infect Dis 15:813-6|
|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|
Showing the most recent 10 out of 16 publications