1887

Abstract

serovar Typhimurium has at least nine multidrug efflux pumps. Among these, AcrAB is constitutively expressed and is the most efficient, playing a role in both drug resistance and virulence. The locus is induced by indole, -conditioned medium, and bile salts. This induction is dependent on RamA through the binding sequence in the upstream region of that binds RamA. In the present study, we made a detailed investigation of the and induction mechanisms in in response to indole, a biological oxidant for bacteria. We found that and induction in response to indole is dependent on RamR. However, the cysteine residues of RamR do not play a role in the induction of in response to indole, and the oxidative effect of indole is therefore not related to induction via RamR. Furthermore, we showed that paraquat, a superoxide generator, induces but not . We further discovered that the mechanism of induction in response to paraquat is dependent on SoxS. The data indicate that there are at least two independent induction pathways for in response to extracellular signals such as indole and paraquat. We propose that utilizes these regulators for induction in response to extracellular signals in order to adapt itself to environmental conditions.

Keyword(s): R6G, rhodamine 6G
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2011-03-01
2024-10-03
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References

  1. Abouzeed Y. M., Baucheron S., Cloeckaert A. 2008; ramR mutations involved in efflux-mediated multidrug resistance in Salmonella enterica serovar Typhimurium. Antimicrob Agents Chemother 52:2428–2434
    [Google Scholar]
  2. Bailey A. M., Paulsen I. T., Piddock L. J. 2008; RamA confers multidrug resistance in Salmonella enterica via increased expression of acrB , which is inhibited by chlorpromazine. Antimicrob Agents Chemother 52:3604–3611
    [Google Scholar]
  3. Bailey A. M., Ivens A., Kingsley R., Cottell J. L., Wain J., Piddock L. J. 2010; RamA, a member of the AraC/XylS family, influences both virulence and efflux in Salmonella enterica serovar Typhimurium. J Bacteriol 192:1607–1616
    [Google Scholar]
  4. Buckley A. M., Webber M. A., Cooles S., Randall L. P., La Ragione R. M., Woodward M. J., Piddock L. J. 2006; The AcrAB-TolC efflux system of Salmonella enterica serovar Typhimurium plays a role in pathogenesis. Cell Microbiol 8:847–856
    [Google Scholar]
  5. Chen H., Hu J., Chen P. R., Lan L., Li Z., Hicks L. M., Dinner A. R., He C. 2008; The Pseudomonas aeruginosa multidrug efflux regulator MexR uses an oxidation-sensing mechanism. Proc Natl Acad Sci U S A 105:13586–13591
    [Google Scholar]
  6. Chinni S. V., Raabe C. A., Zakaria R., Randau G., Hoe C. H., Zemann A., Brosius J., Tang T. H., Rozhdestvensky T. S. 2010; Experimental identification and characterization of 97 novel npcRNA candidates in Salmonella enterica serovar Typhi. Nucleic Acids Res 38:5893–5908
    [Google Scholar]
  7. Datsenko K. A., Wanner B. L. 2000; One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci U S A 97:6640–6645
    [Google Scholar]
  8. Davis R. W., Bolstein D., Roth J. R. 1980 Advanced Bacterial Genetics pp 100–105 Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  9. Elledge S. J., Davis R. W. 1989; Position and density effects on repression by stationary and mobile DNA-binding proteins. Genes Dev 3:185–197
    [Google Scholar]
  10. Fields P. I., Swanson R. V., Haidaris C. G., Heffron F. 1986; Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. Proc Natl Acad Sci U S A 83:5189–5193
    [Google Scholar]
  11. Garbe T. R., Kobayashi M., Yukawa H. 2000; Indole-inducible proteins in bacteria suggest membrane and oxidant toxicity. Arch Microbiol 173:78–82
    [Google Scholar]
  12. Gaudu P., Moon N., Weiss B. 1997; Regulation of the soxRS oxidative stress regulon. Reversible oxidation of the Fe–S centers of SoxR in vivo. J Biol Chem 272:5082–5086
    [Google Scholar]
  13. Hassan H. M., Fridovich I. 1979; Paraquat and Escherichia coli . Mechanism of production of extracellular superoxide radical. J Biol Chem 254:10846–10852
    [Google Scholar]
  14. Hirakawa H., Inazumi Y., Masaki T., Hirata T., Yamaguchi A. 2005; Indole induces the expression of multidrug exporter genes in Escherichia coli . Mol Microbiol 55:1113–1126
    [Google Scholar]
  15. Horiyama T., Nikaido E., Yamaguchi A., Nishino K. 2011; Roles of Salmonella multidrug efflux pumps in tigecycline resistance. J Antimicrob Chemother 66:105–110
    [Google Scholar]
  16. Karlin D. A., Mastromarino A. J., Jones R. D., Stroehlein J. R., Lorentz O. 1985; Fecal skatole and indole and breath methane and hydrogen in patients with large bowel polyps or cancer. J Cancer Res Clin Oncol 109:135–141
    [Google Scholar]
  17. Koronakis V., Sharff A., Koronakis E., Luisi B., Hughes C. 2000; Crystal structure of the bacterial membrane protein TolC central to multidrug efflux and protein export. Nature 405:914–919
    [Google Scholar]
  18. Lacroix F. J., Cloeckaert A., Grepinet O., Pinault C., Popoff M. Y., Waxin H., Pardon P. 1996; Salmonella typhimurium acrB -like gene: identification and role in resistance to biliary salts and detergents and in murine infection. FEMS Microbiol Lett 135:161–167
    [Google Scholar]
  19. Lin J., Michael L. O., Zhang Q. 2002; CmeABC functions as a multidrug efflux system in Campylobacter jejuni . Antimicrob Agents Chemother 46:2124–2131
    [Google Scholar]
  20. Lin J., Cagliero C., Guo B., Barton Y. W., Maurel M. C., Payot S., Zhang Q. 2005; Bile salts modulate expression of the CmeABC multidrug efflux pump in Campylobacter jejuni . J Bacteriol 187:7417–7424
    [Google Scholar]
  21. Ma D., Alberti M., Lynch C., Nikaido H., Hearst J. E. 1996; The local repressor AcrR plays a modulating role in the regulation of acrAB genes of Escherichia coli by global stress signals. Mol Microbiol 19:101–112
    [Google Scholar]
  22. Martin R. G., Gillette W. K., Rosner J. L. 2000; Promoter discrimination by the related transcriptional activators MarA and SoxS: differential regulation by differential binding. Mol Microbiol 35:623–634
    [Google Scholar]
  23. McClelland M., Sanderson K. E., Spieth J., Clifton S. W., Latreille P., Courtney L., Porwollik S., Ali J., Dante M. other authors 2001; Complete genome sequence of Salmonella enterica serovar Typhimurium LT2. Nature 413:852–856
    [Google Scholar]
  24. Miller J. H. 1972 Experiments in Molecular Genetics pp 352–355 Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  25. Murakami S., Nakashima R., Yamashita E., Yamaguchi A. 2002; Crystal structure of bacterial multidrug efflux transporter AcrB. Nature 419:587–593
    [Google Scholar]
  26. Murakami S., Nakashima R., Yamashita E., Matsumoto T., Yamaguchi A. 2006; Crystal structures of a multidrug transporter reveal a functionally rotating mechanism. Nature 443:173–179
    [Google Scholar]
  27. Nikaido H. 1996; Multidrug efflux pumps of gram-negative bacteria. J Bacteriol 178:5853–5859
    [Google Scholar]
  28. Nikaido E., Yamaguchi A., Nishino K. 2008; AcrAB multidrug efflux pump regulation in Salmonella enterica serovar Typhimurium by RamA in response to environmental signals. J Biol Chem 283:24245–24253
    [Google Scholar]
  29. Nishino K., Latifi T., Groisman E. A. 2006; Virulence and drug resistance roles of multidrug efflux systems of Salmonella enterica serovar Typhimurium. Mol Microbiol 59:126–141
    [Google Scholar]
  30. Padilla E., Llobet E., Domenech-Sanchez A., Martinez-Martinez L., Bengoechea J. A., Alberti S. 2010; Klebsiella pneumoniae AcrAB efflux pump contributes to antimicrobial resistance and virulence. Antimicrob Agents Chemother 54:177–183
    [Google Scholar]
  31. Paulsen I. T., Chen J., Nelson K. E., Saier M. H. Jr 2001; Comparative genomics of microbial drug efflux systems. J Mol Microbiol Biotechnol 3:145–150
    [Google Scholar]
  32. Putman M., van Veen H. W., Konings W. N. 2000; Molecular properties of bacterial multidrug transporters. Microbiol Mol Biol Rev 64:672–693
    [Google Scholar]
  33. Randall L. P., Woodward M. J. 2002; The multiple antibiotic resistance ( mar ) locus and its significance. Res Vet Sci 72:87–93
    [Google Scholar]
  34. Rosenberg E. Y., Bertenthal D., Nilles M. L., Bertrand K. P., Nikaido H. 2003; Bile salts and fatty acids induce the expression of Escherichia coli AcrAB multidrug efflux pump through their interaction with Rob regulatory protein. Mol Microbiol 48:1609–1619
    [Google Scholar]
  35. Scherer C. A., Miller S. I. 2001; Molecular pathogenesis of salmonellae. In . Principles of Bacterial Pathogenesis pp 266–333 New York: Academic Press;
    [Google Scholar]
  36. Schneiders T., Amyes S. G., Levy S. B. 2003; Role of AcrR and ramA in fluoroquinolone resistance in clinical Klebsiella pneumoniae isolates from Singapore. Antimicrob Agents Chemother 47:2831–2837
    [Google Scholar]
  37. Sonnenwirth A. C. 1980 The Enteric Bacteria and Bacteroides Philadelphia, PA: Harper & Row;
    [Google Scholar]
  38. Thanassi D. G., Cheng L. W., Nikaido H. 1997; Active efflux of bile salts by Escherichia coli . J Bacteriol 179:2512–2518
    [Google Scholar]
  39. Yanofsky C., Horn V., Gollnick P. 1991; Physiological studies of tryptophan transport and tryptophanase operon induction in Escherichia coli . J Bacteriol 173:6009–6017
    [Google Scholar]
  40. Yu Z., Reichheld S. E., Savchenko A., Parkinson J., Davidson A. R. 2010; A comprehensive analysis of structural and sequence conservation in the TetR family transcriptional regulators. J Mol Biol 400:847–864
    [Google Scholar]
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