An unbiased screen to identify Neisseria gonorrhoeae genes important for survival to neutrophil killing mechanisms

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ABSTRACT The human-restricted Neisseria are a collection of related, host-adapted organisms that show a spectrum of pathogenicity, from true commensals to pathogens. The pathogenic species, Neisseria gonorrhoeae and Neisseria meningitidis, have the ability to switch from a more commensal state to produce host damage. Much of the host damage produced by the pathogenic species is the result of host inflammation, particularly, polymorphonuclear leukocytes (PMNs), and these bacteria have evolved many ways to avoid the antimicrobial functions of PMNs. While many studies have identified a number of bacterial genes and gene products that help the Neisseria resist PMN killing processes, many other bacterial species use these gene to resist PMN activities. I propose to conduct an unbiased, genetic screen for novel factors that allow N. gonorrhoeae to resist killing or growth suppression by PMNs to determine mechanisms that have allowed this pathogenic species to resist control by innate immune responses. This screen will provide preliminary results to uncover new mechanisms of N. gonorrhoeae pathogenesis.