Interaction of Pathogenic Neisseria with Host Defenses What Happens in Vivo?

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Abstract
N. gonorrhoeae initiates infection by adhering to and invading columnar epithelial cells. Over time these activities often induce inflammation, with the influx of neutrophils and serum into the urethral lumen, cervical os, conjunctiva, and the like. At least some of these infected niches contain CMP-NANA (cytidine monophospho-N-acetyl neuraminic acid, also called CMP-sialic), contain sialylated gonococci, and are relatively or strictly anaerobic due to neutrophil and gonococcal metabolism and to the site of disease, that is, the peritoneal cavity. Gonococci thus encounter environmental conditions, reagents, and substrates in the human body that are not normally present in vitro. Knapp and Clark were the first to successfully grow gonococci anaerobically in an easily reproducible system, allowing researchers to begin to investigate in vitro the effects of anaerobiosis on gonococcal virulence traits. As a result of a series of elegant and in depth studies, Smith and Parsons and their colleagues showed that growth in CMP-NANA confers on the gonococcus a high degree of phenotypic (readily reversible) serum resistance and that CMP-NANA is available in vivo at sites of gonococcal infection and disease; gonococci become covalently coated with sialic acid and they become serum resistant (reviewed in refs. 8-10). Given that gonococci growing in the absence of oxygen or in the presence of CMP-NANA probably more closely resemble gonococci growing inside the human host, we studied several possible virulence traits of gonococci cultivated under these conditions. We first observed that anaerobic growth (in the absence of CMP-NANA) increases gonococcal resistance to killing by low (but not high) concentrations of normal human serum. We also asked whether anaerobic growth affected gonococcal association with host cells. Contrary to the effects on serum killing, anaerobic growth (in the absence of CMP-NANA) does not appear to affect the ability of gonococci (expressing certain adhesive outer membrane proteins called Opa proteins) to bind to and enter human epithelial cell lines or to bind to or resist killing by human neutrophils. The results from studies investigating the modulatory role of CMP-NANA were more striking. Growth in CMP-NANA dramatically inhibits the adherence of Opa+ gonococci to human neutrophils. It does not, however, appear to significantly decrease their sensitivity to phagocytic killing or to in vitro killing by lysosomal contents (aqueous extracts of human neutrophil granules).(ABSTRACT TRUNCATED AT 400 WORDS)