title: A requirement of TolC and MDR efflux pumps for acid adaptation and GadAB induction in Escherichia coli.
abstract: BACKGROUND
  The TolC outer membrane channel is a key component of several multidrug resistance (MDR) efflux pumps driven by H(+) transport in Escherichia coli. While tolC expression is under the regulation of the EvgA-Gad acid resistance regulon, the role of TolC in growth at low pH and extreme-acid survival is unknown.
  
  
  RESULTS
  TolC was required for extreme-acid survival (pH 2) of strain W3110 grown aerobically to stationary phase. A tolC deletion decreased extreme-acid survival (acid resistance) of aerated pH 7.0-grown cells by 10(5)-fold and of pH 5.5-grown cells by 10-fold. The requirement was specific for acid resistance since a tolC defect had no effect on aerobic survival in extreme base (pH 10). TolC was required for expression of glutamate decarboxylase (GadA, GadB), a key component of glutamate-dependent acid resistance (Gad). TolC was also required for maximal exponential growth of E. coli K-12 W3110, in LBK medium buffered at pH 4.5-6.0, but not at pH 6.5-8.5. The TolC growth requirement in moderate acid was independent of Gad. TolC-associated pump components EmrB and MdtB contributed to survival in extreme acid (pH 2), but were not required for growth at pH 5. A mutant lacking the known TolC-associated efflux pumps (acrB, acrD, emrB, emrY, macB, mdtC, mdtF, acrEF) showed no growth defect at acidic pH and a relatively small decrease in extreme-acid survival when pre-grown at pH 5.5.
  
  
  CONCLUSIONS
  TolC and proton-driven MDR efflux pump components EmrB and MdtB contribute to E. coli survival in extreme acid and TolC is required for maximal growth rates below pH 6.5. The TolC enhancement of extreme-acid survival includes Gad induction, but TolC-dependent growth rates below pH 6.5 do not involve Gad. That MDR resistance can enhance growth and survival in acid is an important consideration for enteric organisms passing through the acidic stomach.
authors.affiliation: Department of Biology, Kenyon College, Gambier, Ohio, United States of America.
authors.forename: Kari N W
authors.initials: KN
authors.lastname: Deininger
authors.forename: Akina
authors.initials: A
authors.lastname: Horikawa
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Kitko
authors.forename: Ryoko
authors.initials: R
authors.lastname: Tatsumi
authors.forename: Judah L
authors.initials: JL
authors.lastname: Rosner
authors.forename: Masaaki
authors.initials: M
authors.lastname: Wachi
authors.forename: Joan L
authors.initials: JL
authors.lastname: Slonczewski
mesh_terms: D000143:Acids / Q000494:pharmacology*; D000222:Adaptation, Physiological / Q000187:drug effects*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D004790:Enzyme Induction / Q000187:drug effects; D048168:Escherichia coli K12 / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D029968:Escherichia coli Proteins / Q000096:biosynthesis* / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000096:biosynthesis*; D005971:Glutamates / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008565:Membrane Proteins / Q000096:biosynthesis*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D050296:Microbial Viability / Q000187:drug effects; D009154:Mutation / Q000235:genetics
chemical_list: D000143:Acids; D001425:Bacterial Outer Membrane Proteins; D029968:Escherichia coli Proteins; D005971:Glutamates; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C073126:tolC protein, E coli; C121044:gadA protein, E coli; D005968:Glutamate Decarboxylase