Thiolactomycin resistance in Escherichia coli is associated with the multidrug resistance efflux pump encoded by emrAB.
Thiolactomycin (TLM) and cerulenin are antibiotics that block Escherichia coli growth by inhibiting fatty acid biosynthesis at the beta-ketoacyl-acyl carrier protein synthase I step. Both TLM and cerulenin trigger the accumulation of intracellular malonyl-coenzyme A coincident with growth inhibition, and the overexpression of synthase I protein confers resistance to both antibiotics. Strain CDM5 was derived as a TLM-resistant mutant but remained sensitive to cerulenin. TLM neither induced malonyl-coenzyme A accumulation nor blocked fatty acid production in vivo; however, the fatty acid synthase activity in extracts from strain CDM5 was sensitive to TLM inhibition. The TLM resistance gene in strain CDM5 was mapped to 57.5 min of the chromosome and was an allele of the emrB gene. Disruption of the emrB gene converted strain CDM5 to a TLM-sensitive strain, and the overexpression of the emrAB operon conferred TLM resistance to sensitive strains. Thus, activation of the emr efflux pump is the mechanism for TLM resistance in strain CDM5.
Department of Agricultural Chemistry, Faculty of Agriculture, Ibaraki University, Japan.
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H
Furukawa
J T
JT
Tsay
S
S
Jackowski
Y
Y
Takamura
C O
CO
Rock
D001692:Biological Transport; D002569:Cerulenin / Q000494:pharmacology; D002874:Chromosome Mapping; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors; D005798:Genes, Bacterial; D008316:Malonyl Coenzyme A / Q000378:metabolism; D009876:Operon; D013876:Thiophenes / Q000494:pharmacology
D013876:Thiophenes; D002569:Cerulenin; D008316:Malonyl Coenzyme A; C035068:thiolactomycin; D064429:Fatty Acid Synthases