The putative response regulator BaeR stimulates multidrug resistance of Escherichia coli via a novel multidrug exporter system, MdtABC.
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.
Nagakubo
Satoshi
S
Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki-shi, Japan.
Nishino
Kunihiko
K
Hirata
Takahiro
T
Yamaguchi
Akihito
A
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D001647:Bile Acids and Salts / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D029968:Escherichia coli Proteins; D017353:Gene Deletion; D005798:Genes, Bacterial / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D008826:Microbial Sensitivity Tests; D009675:Novobiocin / Q000494:pharmacology; D016366:Open Reading Frames / Q000235:genetics; D018085:Regulon
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001647:Bile Acids and Salts; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; C434281:Mdt-A protein, E coli; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009675:Novobiocin