Brian G Spratt — Page 4

PubMed1998

Loss-of-function mutations in the mtr efflux system of Neisseria gonorrhoeae.

Resistance of Neisseria gonorrhoeae to antimicrobial hydrophobic agents (HAs) has been ascribed to the mtr (multiple transferable resistance) operon. This operon is composed of the mtrR gene, which encodes a transcriptional repressor (MtrR), and a three-gene complex (mtrCDE), which encodes cell envelope proteins (MtrC-MtrD-MtrE) that form an energy-dependent efflux pump. HA-hypersusceptible strains are often isolated from patients, but the genetic basis for such hypersusceptibility was heretofore unknown. The genetic basis of HA hypersusceptibility in laboratory-derived strains BR54 and BR87 was studied to learn if this trait could be linked to mutations in the mtr operon. Mutations in the mtrR gene of these strains that could be phenotypically suppressed by mutations in their mtrC or mtrD genes were identified. Thus, small deletions (4-10 bp) in the mtrC or mtrD genes of strains BR87 and BR54 that would result in the production of truncated efflux pump proteins that serve as a membrane fusion protein (MtrC) or transporter of HAs (MtrD) were found to be responsible for their HA-hypersusceptible property.

Amino Acid Sequence↗

PubMed1997

Arginine-, hypoxanthine-, uracil-requiring isolates of Neisseria gonorrhoeae are a clonal lineage with a non-clonal population.

Multilocus enzyme electrophoresis has shown that a collection of 101 arginine-, hypoxanthine-, uracil-requiring (AHU-) isolates of Neisseria gonorrhoeae, recovered over a 39 year period from the UK and Denmark, were of a single electrophoretic type (91% of strains), or differed from the predominant electrophoretic type at only a single locus. The striking uniformity of the AHU-isolates, and the correlation between auxotype, serovar and overall genetic background, contrasts with previous studies of gonococcal populations (that included very few AHU-strains), and a small sample of non-AHU-isolates studied here, which demonstrated a non-clonal population structure and a lack of association between auxotype, serovar and genetic background. There was no marked difference in the ability of AHU-isolates to be transformed with their own DNA, or with DNA from gonococci of other auxotypes, and the relative genetic stability of AHU-isolates does not appear to be due to a defect in their ability to be transformed. An alternative possibility is that AHU-gonococci recombine with other lineages, but that the resulting recombinants are not maintained in the population. This would occur, for example, if AHU-gonococci competed poorly in mixed infections, within which effective recombination between lineages occurs, and are usually only transmitted from individuals who are singly infected with an AHU-strain. The association between AHU-gonococci and asymptomatic infections may lead to an increased rate of transmission of these strains which under this scenario would be needed to prevent them from being lost from the population.

Arginine↗