title: A pmrA constitutive mutant sensitizes Escherichia coli to deoxycholic acid.
abstract: An Escherichia coli mutant was isolated and shown to be polymyxin B resistant. Mapping and sequence analysis revealed a missense mutation at codon 53 within the pmrA (basR) gene that results in a G-to-V substitution. Fusions of promoters from the pmrC, yibD, and pmrH genes with the lacZ reporter showed that they were constitutively expressed in pmrA53 cells. In pmrA+ strains, these promoters were induced by iron and zinc, while a DeltapmrA mutation blocked induction. The PmrA regulon regulates genes whose products remodel the composition and charge of lipid A and hence the barrier properties of the outer membrane. Along these lines, the pmrA53 mutant was also found to be hypersensitive to the anionic bile detergent deoxycholic acid.
authors.affiliation: Department of Microbiology, Anadys Pharmaceuticals, Inc., 3115 Merryfield Row, San Diego, CA 92121, USA.
authors.forename: Jamie M
authors.initials: JM
authors.lastname: Froelich
authors.forename: Khoa
authors.initials: K
authors.lastname: Tran
authors.forename: Daniel
authors.initials: D
authors.lastname: Wall
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D003840:Deoxycholic Acid / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D015964:Gene Expression Regulation, Bacterial; D008050:Lipid A / Q000737:chemistry; D009154:Mutation; D011112:Polymyxin B / Q000494:pharmacology*
chemical_list: D001426:Bacterial Proteins; D008050:Lipid A; C081902:pmrA protein, Bacteria; D003840:Deoxycholic Acid; D011112:Polymyxin B