RIFAMPIN RESISTANCE IN NEISSERIA-MENINGITIDIS DUE TO ALTERATIONS IN MEMBRANE-PERMEABILITY

Rifampin-resistant (Rif(r)) Neisseria meningitidis strains are known t o have single point mutations in the central conserved regions of the rpoB gene, We have demonstrated two distinct resistance phenotypes in strains with identical mutations in this region, an intermediate level of resistance in Rif(r) clinical isolates and a high level of resista nce in mutants selected in vitro. The possible role of membrane permea bility in the latter was investigated by measuring MICs in the presenc e of Tween 80; values for high-level-resistance mutants were reduced t o intermediate levels, whereas those for intermediate-level-resistance strains were unaffected. The highly resistant mutants were also found to have increased resistance to Triton X-100 and gentian violet. Sequ encing of the meningococcal mtrR gene and its promoter region (which d etermine resistance to hydrophobic agents in Neisseria gonorrhoeae) fr om susceptible or intermediate strains and highly resistant mutants ge nerated from them showed no mutation within this region, Two-dimension al gel electrophoresis of two parent and Rif mutant strains showed ide ntical shifts in the pi of one protein, indicating that differences be tween the parent and the highly Rif(r) mutant are not confined to the rpoB gene, These results indicate that both permeability and rpoB muta tions play a role in determining the resistance of N. meningitidis to rifampin.