title: 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.
abstract: 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.
authors.affiliation: Department of Microbiology, Colorado State University, Fort Collins 80523, USA. hschweizer@vines.colostate.edu
authors.forename: H P
authors.initials: HP
authors.lastname: Schweizer
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002569:Cerulenin / Q000494:pharmacology*; D002876:Chromosomes, Bacterial / Q000187:drug effects; D004352:Drug Resistance, Microbial / Q000235:genetics; D005227:Fatty Acids / Q000096:biosynthesis*; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D005227:Fatty Acids; D013876:Thiophenes; D002569:Cerulenin; C035068:thiolactomycin