title: Pathways Regulating the pbgP Operon and Colistin Resistance in Klebsiella pneumoniae Strains.
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 colistin-resistant derivatives. However, pmrB was significantly upregulated in only two colistin-resistant 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 colistin-resisant K. pneumoniae.
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea.
authors.forename: Myung-Jin
authors.initials: MJ
authors.lastname: Choi
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea.
authors.forename: Sunju
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea.
authors.forename: Kwan Soo
authors.initials: KS
authors.lastname: Ko
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D003091:Colistin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects / Q000235:genetics; D005798:Genes, Bacterial / Q000235:genetics*; D006801:Humans; D007710:Klebsiella Infections / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000235:genetics; D008826:Microbial Sensitivity Tests; D009876:Operon / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003091:Colistin
keywords: Colistin resistance; Klebsiella pneumoniae; two-component regulatory systems