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PMID: 8509326 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Thiolactomycin resistance in Escherichia coli is associated with the multidrug resistance efflux pump encoded by emrAB.

Journal of bacteriology ·Vol. 175 ·No. 12 ·1993-06-00 ·Pages 3723-9

Furukawa H, Tsay JT, Jackowski S, Takamura Y, Rock CO

Abstract

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.

Related Genes
emrA emrB nalB tlmR
MeSH Terms
Biological Transport Cerulenin/pharmacology Chromosome Mapping Drug Resistance, Microbial Escherichia coli/drug effects,genetics Fatty Acid Synthases/antagonists & inhibitors Genes, Bacterial Malonyl Coenzyme A/metabolism Operon Thiophenes/pharmacology
Chemicals
Thiophenes Cerulenin Malonyl Coenzyme A thiolactomycin Fatty Acid Synthases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Furukawa H
Department of Agricultural Chemistry, Faculty of Agriculture, Ibaraki University, Japan.
Tsay J T
Jackowski S
Takamura Y
Rock C O
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33 references, click to expand
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Article Info
Journal
Journal of bacteriology
Abbr.
J Bacteriol
ISSN
0021-9193
DOI
10.1128/jb.175.12.3723-3729.1993
Published
1993-06-00
Pages
3723-9
Language
English
Region
United States
NLM ID
2985120R
PMCID
PMC204787
Subset
IM
Grants
NCI NIH HHS · CA 21765 · United States
NIGMS NIH HHS · GM 34496 · United States
External Links
PubMed source DOI: 10.1128/jb.175.12.3723-3729.1993 PMC Full Text View journal details
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