cis - and trans -Acting Factors Influence Expression of the norM -Encoded Efflux Pump of Neisseria gonorrhoeae and Levels of Gonococcal Susceptibility to Substrate Antimicrobials.

The gonococcal NorM efflux pump exports substrates with a cationic moiety including quaternary ammonium compounds such as berberine (BE) and ethidium bromide (EB) as well as antibiotics such as ciprofloxacin and solithromycin. The gene is part of a four gene operon that is transcribed from a promoter containing a polynucleotide tract of 6 or 7 thymidines (Ts) between the -10 and -35 hexamers; the majority of gonococcal strains analyzed herein contained a T-6 sequence. Primer extension analysis showed that regardless of the length of the poly-T tract, the same transcriptional start site (TSS) was used for expression of Interestingly, the T-6 tract correlated with a higher level of both expression and gonococcal resistance to NorM substrates BE and EB. Analysis of expression of genes downstream of showed that the product of the -like gene has the capacity to activate expression of as well as , which encodes an acetylenolpyroylglucosamine reductase predicted to be involved in the early steps of peptidoglycan synthesis. Moreover, loss of the TetR-like transcriptional regulator modestly increased gonococcal susceptibility to NorM substrates EB and BE. We conclude that both and -acting regulatory systems can regulate expression of the operon and influence levels of gonococcal susceptibility to antimicrobials exported by NorM.