Genomic and Clinical Correlates of Human Bartonella Quintana Infection

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Investigator: Jane Koehler, MD
Sponsor: Burroughs Wellcome Fund

Location(s): United States

Description

Research in my laboratory is focused on defining molecular aspects of Bartonella pathogenesis. Bartonellae are fastidious, gram-negative bacteria that cause opportunistic infection in AIDS patients or cat scratch disease in immunocompetent individuals. Bartonella alternately occupies two disparate niches: either the gastrointestinal tract of poikilothermic, obligately hematophagous arthropods (fleas, lice) where it is attached to the epithelial cells, or the bloodstream of homeothermic mammals (humans, cats) where it is attached to/within erythrocytes or endothelial cells. To survive and persist in these two different niches, bartonellae must induce expression of a different repertoire of genes in response to environmental cues.

Iron availability provides a signal to Bartonella to indicate which niche (arthropod vector or mammalian reservoir) it occupies. When iron availability is limited, e.g., in the mammalian bloodstream, expression of many virulence genes is induced. We are studying the Bartonella virulence genes that are regulated by perturbations in iron concentration to better understand signalling between the mammalian host and Bartonella bacteria.

Bartonellae can persist in the bloodstream of humans for months and reach one million bacteria/ml of blood, with minimal apparent systemic effect. The bartonellae are able to evade the host immune response, and we are investigating the virulence mechanisms of Bartonella that confer this ability to survive and persist in the bloodstream. The elucidation of the mechanisms involved in these host-Bartonella interactions will lead to an improved understanding of Bartonella virulence, as well as of host cellular processes.