Abstract
Overproduction of the response regulator BaeR confers resistance to novobiocin and bile salts in a DeltaacrAB mutant by stimulating drug exporter gene expression. The mdtABC (multidrug transporter ABC, formerly known as yegMNO) genes, which encode a resistance-nodulation-cell division (RND) drug efflux system, are responsible for resistance. The MdtABC system comprises the transmembrane MdtB/MdtC heteromultimer and MdtA membrane fusion protein. MdtAC also confers bile salt, but not novobiocin, resistance. This indicates that the evolution from an MdtC homomultimer to an MdtBC heteromultimer contributed to extend the drug resistance spectrum. A BLAST search suggested that such a heteromultimer-type RND exporter constitutes a unique family among gram-negative organisms.
MeSH Terms
Anti-Bacterial Agents/pharmacology
Bacterial Proteins/genetics
Bile Acids and Salts/pharmacology
Carrier Proteins/genetics
Drug Resistance, Microbial
Drug Resistance, Multiple
Escherichia coli/drug effects,genetics
Escherichia coli Proteins
Gene Deletion
Genes, Bacterial/genetics
Membrane Proteins/genetics
Membrane Transport Proteins
Microbial Sensitivity Tests
Novobiocin/pharmacology
Open Reading Frames/genetics
Regulon
Chemicals
Anti-Bacterial Agents
Bacterial Proteins
Bile Acids and Salts
Carrier Proteins
Escherichia coli Proteins
Mdt-A protein, E coli
Membrane Proteins
Membrane Transport Proteins
Novobiocin
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Nagakubo Satoshi
Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki-shi, Japan.
Nishino Kunihiko
Hirata Takahiro
Yamaguchi Akihito
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