Summary: The transferable ) system of determines levels of gonococcal resistance to hydrophobic agents (HAs), including detergent-like fatty acids and bile salts that bathe certain mucosal surfaces. The genetic organization of the system was determined and found to consist of the gene, which encodes a transcriptional regulator (MtrR), and three tandemly linked genes termed . The genes were organized in the same apparent transcriptional unit, upstream and divergent from the gene. The -encoded proteins of were analogous to a family of bacterial efflux/transport proteins, notably the MexABOprK proteins of and the AcrAE and EnvCD proteins of , that mediate resistance to drugs, dyes, and detergents. Inactivation of the gene resulted in loss of the MtrC lipoprotein and rendered gonococci hypersusceptible to structurally diverse HAs; this revealed the importance of the system in determining HA in gonococci. Further support for a role of the gene complex in determining levels of HA in gonococci was evident when transformants bearing mutations in the gene were analysed. In this respect, missense and null mutations in the gene were found to result in increased levels of MtrC and HA. However, high levels of MtrC and HA, similar to those observed for clinical isolates, were associated with a single bp deletion in a 13 bp inverted repeat sequence that intervened the divergent and genes. We propose that the 13 bp inverted-repeat sequence represents a transcriptional control element that regulates expression of the gene complex, thereby modulating levels of gonococcal susceptibility to HAs.


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