Interactions between histophilus somni (haemophilus somnus) and phagocytic cells

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Histophilus somni is a Gram negative pathogen of cattle capable of causing a variety of diseases, including infections of lung, heart, joints, brain and reproductive tract. The control of H. somni infection has been accomplished through both antibiotic treatment as well as vaccination. However, given that the prevalence of this disease syndrome has been increasing over the past decade, improved control methods are clearly needed. Central to the ability of the organism to cause disease is its capability to evade host innate immune responses, the first line of defense against bacterial pathogens. Specifically, H. somni is able to suppress the antimicrobial activities of leukocytes, including PMNs and macrophages, resulting in enhanced survival of the organism and dissemination throughout the body. It is our hypothesis that H. somni produces specific proteins capable of modifying the host innate immune response, resulting in a general suppression. In order to test this hypothesis, we will characterize new proteins produced by the bacterium while it is incubated with bovine leukocytes using both functional genomic as well as traditional protein biochemistry techniques. These proteins will be fully characterized and the genes coding for each one isolated and used to construct mutant H. somni lacking each specific gene. These will then be tested for their ability to interfere with PMN function. Finally, we will test the ability of these mutants to cause disease in a bovine infection model. Ultimately, this will lead to the development of novel targets for both vaccine and therapeutic development.