Ke. Hagman et al., RESISTANCE OF NEISSERIA-GONORRHOEAE TO ANTIMICROBIAL HYDROPHOBIC AGENTS IS MODULATED BY THE MTRRCDE EFFLUX SYSTEM, Microbiology, 141, 1995, pp. 611-622
The mtr (multiple transferable resistance) system of Neisseria gonorrh
oeae 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 mtr system w
as determined and found to consist of the mtrR gene, which encodes a t
ranscriptional regulator (MtrR), and three tandemly linked genes terme
d mtrCDE. The mtrCDE genes were organized in the same apparent transcr
iptional unit, upstream and divergent from the mtrR gene. The mtrCDE-e
ncoded proteins of N. gonorrhoeae were analogous to a family of bacter
ial efflux/transport proteins, notable the MexABOprK proteins of Pseud
omonas aeruginosa and the AcrAE and EnvCD proteins of Escherichia coli
, that mediate resistance to drugs, dyes, and detergents. Inactivation
of the mtrC gene resulted in loss of the MtrC lipoprotein and rendere
d gonococci hypersusceptible to structurally diverse HAs; this reveale
d the importance of the mtr system in determining HA(R) in gonococci.
Further support for a role of the mtrCDE gene complex in determining l
evels of HA(R) in gonococci was evident when transformants bearing mut
ations in the mtrR gene were analysed. In this respect, missense and a
nd null mutations in the mtrR gene were found to result in increased l
evels of MtrC and HA(R). However, high levels of MtrC and HA(R), simil
ar to those observed for clinical isolates, were associated with a sin
gle bp deletion in a 13 bp inverted repeat sequence that intervened th
at divergent mtrR and mtrC genes. We propose that the 13 bp inverted-r
epeat sequence represents a transcriptional control element that regul
ates expression of the mtrRCDE gene complex, thereby modulating levels
of gonococcal susceptibility to HAs.