Back to Search
Start Over
Members of the conserved DedA family are likely membrane transporters and are required for drug resistance in Escherichia coli.
- Source :
-
Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2014; Vol. 58 (2), pp. 923-30. Date of Electronic Publication: 2013 Nov 25. - Publication Year :
- 2014
-
Abstract
- Bacterial resistance to antibiotics and biocides is an increasing public health problem. Genes encoding integral membrane proteins belonging to the DedA family are present in most bacterial genomes, including Escherichia coli. An E. coli strain lacking partially redundant DedA family genes yqjA and yghB (strain BC202) displays temperature sensitivity and cell division defects. These phenotypes can be corrected by overexpression of mdfA, an Na(+)-K(+)/H(+) antiporter of the major facilitator superfamily. We show that BC202 is hypersensitive to several biocides and cationic compounds that are known substrates of several multidrug resistance transporters, including MdfA, EmrE, and AcrB. The introduction of deletions of genes encoding these drug transporters into BC202 results in additional sensitivity. Expression of wild-type yghB or yqjA can restore drug resistance, but this is eliminated upon mutation of two membrane-embedded acidic amino acids (E39 or D51 in either protein). This dependence upon membrane-embedded acidic amino acids is a hallmark of proton-dependent antiporters. Overexpression of mdfA in BC202 or artificially restoring proton motive force (PMF) restores wild-type resistance to substrates of MdfA as well as other drug resistance transporters such as EmrE and AcrAB. These results suggest that YqjA and YghB may be membrane transporters required for PMF-dependent drug efflux in E. coli.
- Subjects :
- Amino Acid Sequence
Anti-Bacterial Agents pharmacology
Antiporters genetics
Antiporters metabolism
Cell Division
Drug Resistance, Bacterial drug effects
Escherichia coli drug effects
Escherichia coli metabolism
Escherichia coli Proteins genetics
Escherichia coli Proteins metabolism
Lipoproteins genetics
Lipoproteins metabolism
Membrane Proteins genetics
Membrane Proteins metabolism
Membrane Transport Proteins genetics
Membrane Transport Proteins metabolism
Microbial Sensitivity Tests
Molecular Sequence Data
Multidrug Resistance-Associated Proteins genetics
Multidrug Resistance-Associated Proteins metabolism
Mutation
Proton-Motive Force drug effects
Sequence Alignment
Conserved Sequence
Drug Resistance, Bacterial genetics
Escherichia coli genetics
Gene Expression Regulation, Bacterial
Proton-Motive Force genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1098-6596
- Volume :
- 58
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Antimicrobial agents and chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 24277026
- Full Text :
- https://doi.org/10.1128/AAC.02238-13