A Klebsiella pneumoniae antibiotic resistance mechanism that subdues host defences and promotes virulence

Timothy J Kidd, Grant Mills, Joana Sá-Pessoa, Amy Dumigan, Christian G Frank, Jose Luis Insua Romero, Rebecca Ingram, Laura Hobley, José A Bengoechea

Research output: Contribution to journalArticlepeer-review

63 Citations (Scopus)
417 Downloads (Pure)

Abstract

Klebsiella pneumoniae is an important cause of multidrug-resistant infections worldwide. Recent studies highlight the emergence of multidrug-resistant K. pneumoniae strains which show resistance to colistin, a last-line antibiotic, arising from mutational inactivation of the mgrB regulatory gene. However, the precise molecular resistance mechanisms of mgrB-associated colistin resistance and its impact on virulence remain unclear. Here, we constructed an mgrB gene K. pneumoniae mutant and performed characterisation of its lipid A structure, polymyxin and antimicrobial peptide resistance, virulence and inflammatory responses upon infection. Our data reveal that mgrB mutation induces PhoPQ-governed lipid A remodelling which confers not only resistance to polymyxins, but also enhances K. pneumoniae virulence by decreasing antimicrobial peptide susceptibility and attenuating early host defence response activation. Overall, our findings have important implications for patient management and antimicrobial stewardship, while also stressing antibiotic resistance development is not inexorably linked with subdued bacterial fitness and virulence.

Original languageEnglish
Pages (from-to)430
JournalEMBO Molecular Medicine
Volume9
Issue number2
Early online date15 Feb 2017
DOIs
Publication statusEarly online date - 15 Feb 2017

Keywords

  • Journal Article

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