Role of Vomp Adhesins in Bartonella quintana Pathogenesis
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Bartonella quintana is a disease-causing bacterium that is carried and spread between people by the human body louse. Transmitted by a louse bite, the bacteria gains access to the host's bloodstream, where it can persist and cause disease for very long periods of time, from weeks to even months. Patients residing in poor hygienic conditions, including alcoholic and homeless people, are at particular risk for this infection. In patients with compromised immune systems, such as AIDS patients, the bacteria can cause a severe, or even fatal, opportunistic infection. The bacteria cause unique lesions, known as bacillary angiomatosis, throughout the body, affection both organs and skin of patients co-infected with HIV and Bartonella. Administration of antibiotics is important for these patients, although no diagnostic test is currently available, so the disease is frequently undiagnosed. The spectrum of the disease and the number of people infected remain unknown. Recently it was shown that many AIDS patients in San Francisco that have fevers of unknown origin, are infected with B. quintana. Because the bacteria was only identified in the past 10 years, very little is known about how it causes disease. The research proposed here involves further studying of four B. quintana genes (designated Vomp) that were identified in this laboratory, and are thought to have a major role in pathogenesis. They were originally identified as four proteins that disappeared upon infection of an animal model host, possibly because of a strong immune reaction to them. Closer study of these proteins suggested that they have multiple functions, including autoaggregation (self binding), binding to host red blood cells, and binding to host proteins, such as collagen. Such properties indicate that these proteins are important for the interaction of the bacteria with its host. The Vomp were also found to be highly similar to an adhesin protein from another well-characterized pathogen, Yersinia. The Vomp genes are thought to be important for the adherence and possibly the invasion of the bacteria into red blood cells, possibly contributing to the bacteria's ability to "hide" from the immune system. We have recently developed the first known example of directed mutagenesis of specific, targeted genes in B. quintana. This technique allows us to selectively remove the Vomp genes from the bacterial genome, and to assess the consequences in the mutated strain. The ability of the strain lacking the Vomp genes is currently being assessed within an animal model of B. quintana infection, the rhesus macaque. The ability of the Vomp mutant to cause disease, establish infection, and to elicit an immune response from the animal host will all be assessed. In addition, other characteristics of this mutant will be studied, including its ability to bind to red blood cells and to interact with other host cells. The interaction between the mutant and red blood cells will also be compared in detail to the normal, wild type strain, by close examination using advanced microscopy techniques, which will allow us to follow the interaction (i.e., adherence and invasion) in detail in real time. The proposed research is designed to shed further light on how the emerging pathogen B. quintana is able to successfully infect its human host, persist for long periods of time, and cause the lesions characteristic of B. quintana infection.