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Many strains of Pseudomonas aeruginosa are resistant to the antibiotics cerulenin and thiolactomycin, potent inhibitors of bacterial fatty acid biosynthesis. A novel yeast Flp recombinase-based technique was used to isolate an unmarked mexAB-oprM deletion encoding an efflux system mediating resistance to multiple antibiotics in P. aeruginosa. The experiments showed that the MexAB-OprM system is responsible for the intrinsic resistance of this bacterium to cerulenin and thiolactomycin. Whereas thiolactomycin was not a substrate of the MexCD-OprJ pump expressed in a delta(mexAB-oprM) nfxB mutant, cerulenin was efficiently effluxed by the MexCD-OprJ system. It was also found that the MexAB-OprM system is capable of efflux of irgasan, a broad-spectrum antimicrobial compound used in media selective for Pseudomonas.

antimicrobial agents and chemotherapy

Intrinsic Resistance to Inhibitors of Fatty Acid Biosynthesis in <i>Pseudomonas aeruginosa</i> Is Due to Efflux: Application of a Novel Technique for Generation of Unmarked Chromosomal Mutations for the Study of Efflux Systems

Intrinsic Resistance to Inhibitors of Fatty Acid Biosynthesis in Pseudomonas aeruginosa Is Due to Efflux: Application of a Novel Technique for Generation of Unmarked Chromosomal Mutations for the Study of Efflux Systems