Induction of the mtrCDE-encoded efflux pump system of Neisseria gonorrhoeae requires MtrA, an AraC-like protein

The mtr(multiple transferable resistance) gene complex in Neisseria gonorrh oeae encodes an energy-dependent efflux pump composed of the MtrC-MtrD-MtrE cell envelope proteins that serves to export structurally diverse antimicr obial, hydrophobic agents (HAs). Many of these agents have membrane-acting detergent activity. Using Triton X-100 (TX-100) as a representative HA, we found that the mtrCDE efflux pump operon could be induced to higher levers of expression when an HA-sensitive strain was exposed to sublethal concentr ations of this non-ionic detergent and the structurally related spermicide, nonoxynol-9. This induction was at the level of mtrCDE gene transcription and was independent of the MtrR repressor, which normally decreases mtrCDE gene expression. However, the enhanced resistance of gonococci to TX-100 wa s dependent on the expression of a previously undescribed gonococcal protei n that belonged to the AraC/XylS family of transcriptional activators. We h ave termed this protein MtrA to signify its likely role in the activation o f mtrCDE gene expression. Taken together with previous studies dealing with the genetic control of mtrCDE gene expression, we propose that gonococci c an modulate their resistance to HAs through both positive and negative tran scriptional control processes. The action of these regulatory processes is probably of importance in determining the survival capacity of gonococci at mucosal surfaces that contain detergent-like HAs.