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Pathways Regulating the pbgP Operon and Colistin Resistance in Klebsiella pneumoniae Strains

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In this study, we investigated colistin resistance mechanisms associated with the regulation of the pbgP operon in Klebsiella pneumoniae, using four isogenic pairs of colistin-susceptible strains and their colistin-resistant derivatives and two colistin-resistant clinical isolates. Amino acid sequence alterations of PhoPQ, PmrAB, and MgrB were investigated, and mRNA expression levels of phoQ, pmrB, pmrD, and pbgP were measured using quantitative real-time PCR. The phoQ and pmrB genes were deleted from two colistin-resistant derivatives, 134R and 063R. We found that phoQ, pmrD, and pbgP were significantly upregulated in all colistinresistant derivatives. However, pmrB was significantly upregulated in only two colistinresistant derivatives and one clinical strain. pmrB was not overexpressed in the other strains. The minimum inhibitory concentration of colistin was drastically lower in both phoQ- and pmrB-deleted mutants from a colistin-resistant derivative (134R) that was overexpressing phoQ and pmrB. However, colistin susceptibility was restored only in a phoQ-deleted mutant from a colistin-resistant derivative (063R) without overexpression of pmrB. In conclusion, two different regulations of the pbgP operon may associate with the development of colistinresisant K. pneumoniae.

Abstract

In this study, we investigated colistin resistance mechanisms associated with the regulation of the pbgP operon in Klebsiella pneumoniae, using four isogenic pairs of colistin-susceptible strains and their colistin-resistant derivatives and two colistin-resistant clinical isolates. Amino acid sequence alterations of PhoPQ, PmrAB, and MgrB were investigated, and mRNA expression levels of phoQ, pmrB, pmrD, and pbgP were measured using quantitative real-time PCR. The phoQ and pmrB genes were deleted from two colistin-resistant derivatives, 134R and 063R. We found that phoQ, pmrD, and pbgP were significantly upregulated in all colistinresistant derivatives. However, pmrB was significantly upregulated in only two colistinresistant derivatives and one clinical strain. pmrB was not overexpressed in the other strains. The minimum inhibitory concentration of colistin was drastically lower in both phoQ- and pmrB-deleted mutants from a colistin-resistant derivative (134R) that was overexpressing phoQ and pmrB. However, colistin susceptibility was restored only in a phoQ-deleted mutant from a colistin-resistant derivative (063R) without overexpression of pmrB. In conclusion, two different regulations of the pbgP operon may associate with the development of colistinresisant K. pneumoniae.

참고문헌 (30)

  1. Adams MD, "Resistance to colistin in Acinetobacter baumannii associated with mutations in the PmrAB two-component system. Antimicrob", Agents Chemother, 53, pp.3628~3634 (2009)
  2. Cannatelli A, "In vivo emergence of colistin resistance in Klebsiella pneumoniae producing KPC-type carbapenemases mediated by insertional inactivation of the PhoQ", PhoP mgrB regulator, 2013, pp.57, 5521~5526
  3. Cannatelli A, "MgrB inactivation is a common mechanism of colistin resistance in KPC-producing Klebsiella pneumoniae of clinical origin. Antimicrob", Agents Chemother, 58, pp.5696~5703 (2014)
  4. Cannatelli A, "In vivo evolution to colistin resistance by PmrB sensor kinase mutation in KPC-producing Klebsiella pneumoniae is associated with low-dosage colistin treatment", Antimicrob. Agents Chemother, 58, pp.4399~4403 (2014)
  5. Cheng HY, "Molecular characterization of the PhoPQ-PmrD-PmrAB-mediated pathway regulating polymyxin B resistance in Klebsiella pneumoniae CG43", J. Biomed. Sci, 17, pp.60~ (2010)
  6. Choi MJ, "Loss of hypermucoviscosity and increased fitness cost in colistin-resistant Klebsiella pneumoniae sequence type 23 strains", Antimicrob. Agents Chemother, 59, pp.6763~6773 (2015)
  7. Clements A, "Secondary acylation of Klebsiella pneumoniae lipopolysaccharide contributes to sensitivity to antibacterial peptides", J. Biol. Chem, 282, pp.15569~15577 (2007)
  8. Clinical and Laboratory Standards Institute, "Performance Standards for Antimicobial Susceptibility Testing", Wayne, ~ (2015)
  9. Diancourt L, "Multilocus sequence typing of Klebsiella pneumoniae nosocomial isolates", J. Clin. Microbiol, 43, pp.4178~4182 (2005)
  10. Edwards RA, "Improved allelic exchange vectors and their use to analyze 987P fimbria gene expression", Gene, 207, pp.149~157 (1998)
  11. Falagas ME, "Colistin: the revival of polymyxins for the management of multidrug-resistant gramnegative bacterial infections", Clin. Infect. Dis, 40, pp.1333~1341 (2005)
  12. Falagas ME, "Antibiotic treatment of infections due to carbapenem-resistant Enterobacteriaceae: systematic evaluation of the available evidence", Antimicrob. Agents Chemother, 58, pp.654~663 (2014)
  13. Goel G, "Colistin-resistant Klebsiella pneumoniae: report of a cluster of 24 cases from a new oncology center in eastern India. Infect. Control Hosp", Epidemiol, 35, pp.1076~1077 (2014)
  14. Jayol A, "Heteroresistance to colistin in Klebsiella pneumoniae associated with alterations in the PhoPQ regulatory system", Antimicrob. Agents Chemother, 59, pp.2780~2784 (2015)
  15. Jayol A, "Resistance to colistin associated with a single amino acid change in protein PmrB among Klebsiella pneumoniae isolates of worldwide origin", Antimicrob. Agents Chemother, 58, pp.4762~4766 (2014)
  16. Lee JH, "Versatile PCRmediated insertion or deletion mutagenesis", Biotechniques, 36, pp.398~400 (2004)
  17. Li J, "Evaluation of colistin as an agent against multi-resistant gram-negative bacteria", Int. J. Antimicrob. Agents, 25, pp.11~25 (2005)
  18. Llobet E, "Analysis of the networks controlling the antimicrobialpeptide-dependent induction of Klebsiella pneumoniae virulence factors", Infect. Immun, 79, pp.3718~3732 (2011)
  19. Mitrophanov AY, "Evolution and dynamics of regulatory architectures controlling polymyxin B resistance in enteric bacteria", PLoS Genet, 4, pp.e1000233~ (2008)
  20. Monaco M, "Colistin resistance superimposed to endemic carbapenem-resistant Klebsiella pneumoniae: a rapidly evolving problem in Italy", Euro. Surveill, 19, pp.pii=20939~ (2014)
  21. Nation RL, "Colistin in 21st century", Curr. Opin. Infect. Dis, 22, pp.535~543 (2009)
  22. Nordmann P, "Global spread of carbapenemase-producing Enterobacteriaceae", Emerg. Infect. Dis, 17, pp.1791~1798 (2011)
  23. Olaitan AO, "Worldwide emergence of colistin resistance in Klebsiella pneumoniae from healthy humans and patients in Lao PDR, Thailand, Israel, Nigeria and France owing to inactivation of the PhoP", PhoQ regulator mgrB: an epidemiological and molecular study, 2014, pp.44, 500~507
  24. Podschun R, "Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors", Clin. Microbiol. Rev, 11, pp.589~603 (1998)
  25. Poirel L, "The mgrB gene as a key target for acquired resistance to colistin in Klebsiella pneumoniae", J. Antimicrob. Chemother, 70, pp.75~80 (2015)
  26. Snitkin ES, "Tracking a hospital outbreak of carbapenem-resistant Klebsiella pneumoniae with whole-genome sequencing", Sci. Transl. Med, 4, pp.148ra116~ (2012)
  27. Song JH, "Detection of essential genes in Streptococcus pneumoniae using bioinformatics and allelic replacement mutagenesis", Methods Mol. Biol, 416, pp.401~408 (2008)
  28. Suh JY, "Nonclonal emergence of colistin-resistant Klebsiella pneumoniae isolates from blood samples in South Korea", Antimicrob. Agents Chemother, 54, pp.560~562 (2010)
  29. Winfield MD, "Phenotypic differences between Salmonella and Escherichia coli resulting from the disparate regulation of homologous genes", Proc. Natl. Acad. Sci. USA, 101, pp.17162~17167 (2004)
  30. Wright MS, "Genomic and transcriptomic analyses of colistin-resistant clinical isolates of Klebsiella pneumoniae reveal multiple pathways of resistance", Antimicrob. Agents Chemother, 59, pp.536~543 (2015)

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