Alkalitolerance: a biological function for a multidrug transporter in pH homeostasis

Proceedings of the National Academy of Sciences of the United States of America
Oded LewinsonEitan Bibi

Abstract

MdfA is an Escherichia coli multidrug-resistance transporter. Cells expressing MdfA from a multicopy plasmid exhibit multidrug resistance against a diverse group of toxic compounds. In this article, we show that, in addition to its role in multidrug resistance, MdfA confers extreme alkaline pH resistance and allows the growth of transformed cells under conditions that are close to those used normally by alkaliphiles (up to pH 10) by maintaining a physiological internal pH. MdfA-deleted E. coli cells are sensitive even to mild alkaline conditions, and the wild-type phenotype is restored fully by MdfA expressed from a plasmid. This activity of MdfA requires Na(+) or K(+). Fluorescence studies with inverted membrane vesicles demonstrate that MdfA catalyzes Na(+)- or K(+)-dependent proton transport, and experiments with reconstituted proteoliposomes confirm that MdfA is solely responsible for this phenomenon. Studies with multidrug resistance-defective MdfA mutants and competitive transport assays suggest that these activities of MdfA are related. Together, the results demonstrate that a single protein has an unprecedented capacity to turn E. coli from an obligatory neutrophile into an alkalitolerant bacterium, and they suggest a p...Continue Reading

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Feb 13, 2003·Proceedings of the National Academy of Sciences of the United States of America·Oded LewinsonEitan Bibi

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Citations

Jun 28, 2005·Extremophiles : Life Under Extreme Conditions·Talia H SwartzTerry Ann Krulwich
Jun 15, 2005·Nature Reviews. Microbiology·Terry A KrulwichEitan Bibi
Apr 6, 2011·Nature Reviews. Microbiology·Terry A KrulwichEtana Padan
Jul 18, 2012·Proceedings of the National Academy of Sciences of the United States of America·Osnat TiroshEitan Bibi
Jun 26, 2012·The Journal of Biological Chemistry·Theresia A SchaedlerHendrik W van Veen
Jul 25, 2012·Genome Research·Tim van Opijnen, Andrew Camilli
Jul 1, 2009·Antimicrobial Agents and Chemotherapy·Santiago Ramón-GarcíaJosé A Aínsa
Dec 24, 2011·Applied and Environmental Microbiology·Charlotte Tandrup RiedelLone Brøndsted
Jul 14, 2009·Journal of Bacteriology·Paula V WelanderDianne K Newman
Oct 23, 2012·Journal of Bacteriology·William T DoerrlerLisa A Boughner
Feb 24, 2009·Annual Review of Biochemistry·Hiroshi Nikaido
Oct 6, 2007·Biological & Pharmaceutical Bulletin·Yu PingTomofusa Tsuchiya
Mar 3, 2009·Biological & Pharmaceutical Bulletin·Toshihiro NishiokaTomofusa Tsuchiya
Aug 12, 2010·Bioscience, Biotechnology, and Biochemistry·Ryo TakeshitaMasaaki Wachi
Aug 8, 2007·Proceedings of the National Academy of Sciences of the United States of America·Makoto FujisawaTerry A Krulwich
Nov 15, 2007·Proceedings of the National Academy of Sciences of the United States of America·Minghui XiangRajini Rao
Feb 10, 2006·Proceedings of the National Academy of Sciences of the United States of America·Shirley YangE Lynn Zechiedrich
Apr 2, 2014·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·Dongguo WangYongxiao Qi
Jan 31, 2015·International Journal of Environmental Research and Public Health·Jody L AndersenManuel F Varela
Aug 4, 2015·Protein Science : a Publication of the Protein Society·Xuejun C ZhangDaohua Jiang
Jul 22, 2006·Molecular Microbiology·Oded LewinsonEitan Bibi
Aug 6, 2013·Journal of Medical Microbiology·Dongguo WangYongxiao Qi
Nov 10, 2005·Biochimica Et Biophysica Acta·Etana PadanTerry A Krulwich

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