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Article: The multidrug efflux pump MdtEF protects against nitrosative damage during the anaerobic respiration in Escherichia coli

TitleThe multidrug efflux pump MdtEF protects against nitrosative damage during the anaerobic respiration in Escherichia coli
Authors
Issue Date2011
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 2011, v. 286 n. 30, p. 26576-26584 How to Cite?
AbstractDrug efflux represents an important protection mechanism in bacteria to withstand antibiotics and environmental toxic substances. Efflux genes constitute 6-18% of all transporters in bacterial genomes, yet the expression and functions of only a handful of them have been studied. Among the 20 efflux genes encoded in the Escherichia coli K-12 genome, only the AcrAB-TolC system is constitutively expressed. The expression, activities, and physiological functions of the remaining efflux genes are poorly understood. In this study we identified a dramatic up-regulation of an additional efflux pump, MdtEF, under the anaerobic growth condition of E. coli, which is independent of antibiotic exposure. We found that expression of MdtEF is upregulated more than 20-fold under anaerobic conditions by the global transcription factor ArcA, resulting in increased efflux activity and enhanced drug tolerance in anaerobically grown E. coli. Cells lacking mdtEF display a significantly decreased survival rate under the condition of anaerobic respiration of nitrate. Deletion of the genes responsible for the biosynthesis of indole, tnaAB, or replacing nitrate with fumarate as the terminal electron acceptor during the anaerobic respiration restores the decreased survival of ΔmdtEF cells. Moreover, ΔmdtEF cells are susceptible to indole nitrosative derivatives, a class of toxic byproducts formed and accumulated within E. coli when the bacterium respires nitrate under anaerobic conditions. Taken together, we conclude that the multidrug efflux pump MdtEF is up-regulated during the anaerobic physiology of E. coli to protect the bacterium from nitrosative damage through expelling the nitrosyl indole derivatives out of the cells. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/138976
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong General Research FundHKU 781509M
Network Joint Research Center for Materials and Devices
Japan Society for the Promotion of Science
Ministry of Education, Culture, Sports, Science, and Technology of Japan
Funding Information:

This work was supported by the Hong Kong General Research Fund (HKU 781509M; to A. Y.) and by the Cooperative Research Program of "Network Joint Research Center for Materials and Devices" (to A. Y. and K. N.) as well as grants from the Japan Society for the Promotion of Science and the Ministry of Education, Culture, Sports, Science, and Technology of Japan (to K. N.).

References
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DC FieldValueLanguage
dc.contributor.authorZhang, Yen_HK
dc.contributor.authorXiao, Men_HK
dc.contributor.authorHoriyama, Ten_HK
dc.contributor.authorZhang, Yen_HK
dc.contributor.authorLi, Xen_HK
dc.contributor.authorNishino, Ken_HK
dc.contributor.authorYan, Aen_HK
dc.date.accessioned2011-09-23T05:43:32Z-
dc.date.available2011-09-23T05:43:32Z-
dc.date.issued2011en_HK
dc.identifier.citationJournal Of Biological Chemistry, 2011, v. 286 n. 30, p. 26576-26584en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/138976-
dc.description.abstractDrug efflux represents an important protection mechanism in bacteria to withstand antibiotics and environmental toxic substances. Efflux genes constitute 6-18% of all transporters in bacterial genomes, yet the expression and functions of only a handful of them have been studied. Among the 20 efflux genes encoded in the Escherichia coli K-12 genome, only the AcrAB-TolC system is constitutively expressed. The expression, activities, and physiological functions of the remaining efflux genes are poorly understood. In this study we identified a dramatic up-regulation of an additional efflux pump, MdtEF, under the anaerobic growth condition of E. coli, which is independent of antibiotic exposure. We found that expression of MdtEF is upregulated more than 20-fold under anaerobic conditions by the global transcription factor ArcA, resulting in increased efflux activity and enhanced drug tolerance in anaerobically grown E. coli. Cells lacking mdtEF display a significantly decreased survival rate under the condition of anaerobic respiration of nitrate. Deletion of the genes responsible for the biosynthesis of indole, tnaAB, or replacing nitrate with fumarate as the terminal electron acceptor during the anaerobic respiration restores the decreased survival of ΔmdtEF cells. Moreover, ΔmdtEF cells are susceptible to indole nitrosative derivatives, a class of toxic byproducts formed and accumulated within E. coli when the bacterium respires nitrate under anaerobic conditions. Taken together, we conclude that the multidrug efflux pump MdtEF is up-regulated during the anaerobic physiology of E. coli to protect the bacterium from nitrosative damage through expelling the nitrosyl indole derivatives out of the cells. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.en_HK
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_HK
dc.relation.ispartofJournal of Biological Chemistryen_HK
dc.rightsJournal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc.en_US
dc.subject.meshDNA Damage - physiology-
dc.subject.meshEscherichia coli K12 - genetics - metabolism-
dc.subject.meshEscherichia coli Proteins - genetics - metabolism-
dc.subject.meshGene Expression Regulation, Bacterial - physiology-
dc.subject.meshMembrane Proteins - genetics - metabolism-
dc.titleThe multidrug efflux pump MdtEF protects against nitrosative damage during the anaerobic respiration in Escherichia colien_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9258&volume=286&spage=26576&epage=26584&date=2011&atitle=The+multidrug+efflux+pump+MdtEF+protects+against+nitrosative+damage+during+the+anaerobic+respiration+in+escherichia+colien_US
dc.identifier.emailLi, X: xuechenl@hku.hken_HK
dc.identifier.emailYan, A: ayan8@hku.hken_HK
dc.identifier.authorityLi, X=rp00742en_HK
dc.identifier.authorityYan, A=rp00823en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1074/jbc.M111.243261en_HK
dc.identifier.pmid21642439-
dc.identifier.pmcidPMC3143622-
dc.identifier.scopuseid_2-s2.0-79960692460en_HK
dc.identifier.hkuros193390en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79960692460&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume286en_HK
dc.identifier.issue30en_HK
dc.identifier.spage26576en_HK
dc.identifier.epage26584en_HK
dc.identifier.eissn1083-351X-
dc.identifier.isiWOS:000293078200036-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectTranscriptional regulation of multidrug resistance genes by anaerobic adaptation in Escherichia coli-
dc.identifier.scopusauthoridZhang, Y=53265596200en_HK
dc.identifier.scopusauthoridXiao, M=53265495200en_HK
dc.identifier.scopusauthoridHoriyama, T=36518795900en_HK
dc.identifier.scopusauthoridZhang, Y=36197722200en_HK
dc.identifier.scopusauthoridLi, X=24168958800en_HK
dc.identifier.scopusauthoridNishino, K=7102938399en_HK
dc.identifier.scopusauthoridYan, A=8621667000en_HK

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