MISSENSE MUTATIONS THAT ALTER THE DNA-BINDING DOMAIN OF THE MTRR PROTEIN OCCUR FREQUENTLY IN RECTAL ISOLATES OF NEISSERIA-GONORRHOEAE THAT ARE RESISTANT TO FECAL LIPIDS

Resistance of Neisseria gonorrhoeae to structurally diverse hydrophobi c agents (HAs) has been associated with missense or deletion mutations in the mtrR (multiple transferable resistance Regulator) gene of labo ratory-derived strains but their prevalence in clinical isolates was h eretofore unknown. Since faecal lipids provide strong selective pressu re for the emergence of variants resistant to HAs (HA(R)), the nucleot ide sequence of the mfrR gene from rectal isolates of N. gonorrhoeae, which displayed different levels of HA(R), was determined. Compared to the mtrR gene possessed by the HA-sensitive strain FA19, each clinica l isolate contained mutations in the coding and/or promoter regions of their mtrR gene. A missense mutation in codon 45 (Cry-45 to Asp) was the most common mutation found in the strains studied and impacted the structure of the helix-turn-helix domain of the MtrR protein thought to be important in DNA-binding activity. Two clinical isolates bearing a missense mutation in codon 45 also contained a single basepair dele tion in a 13 bp inverted sequence positioned within the mtrR promoter region, Introduction of mfrR sequences amplified from the clinical iso lates into strain FA19 revealed that acquisition of the single basepai r deletion was correlated with high level HA(R) while mutations in the mtrR-coding region provided for an intermediate level of HA(R).