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)