title: The multidrug efflux pump MdtEF protects against nitrosative damage during the anaerobic respiration in Escherichia coli.
abstract: Drug 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 up-regulated 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.
authors.affiliation: School of Biological Sciences, University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.
authors.forename: Yiliang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Minfeng
authors.initials: M
authors.lastname: Xiao
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Horiyama
authors.forename: Yinfeng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xuechen
authors.initials: X
authors.lastname: Li
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Nishino
authors.forename: Aixin
authors.initials: A
authors.lastname: Yan
mesh_terms: D000693:Anaerobiosis / Q000502:physiology; D004249:DNA Damage / Q000502:physiology*; D048168:Escherichia coli K12 / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005650:Fumarates / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D016680:Genome, Bacterial / Q000502:physiology; D055106:Genome-Wide Association Study; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009566:Nitrates / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins; D005650:Fumarates; C477834:MdtE protein, E coli; C477833:MdtF protein, E coli; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009566:Nitrates