MgrB inactivation is a common mechanism of colistin resistance in KPC-producing Klebsiella pneumoniae of clinical origin

Antonio Cannatelli, Tommaso Giani, Marco M aria D'Andrea, Vincenzo Di Pilato, Fabio Arena, Viola Conte, Kyriaki Tryfinopoulou, Alkiviadis Vatopoulos, Gian M aria Rossolini, COLGRIT Study Group

Research output: Contribution to journalArticle

Abstract

Klebsiella pneumoniae strains producing KPC-type carbapenemases (KPC-KP) are challenging multidrug-resistant pathogens due to their extensively drug-resistant phenotypes and potential for epidemic dissemination in health care settings. Colistin is a key component of the combination antimicrobial regimens used for treatment of severe KPC-KP infections. We previously reported that insertional inactivation of the mgrB gene, encoding a negative-feedback regulator of the PhoQ-PhoP signaling system, can be responsible for colistin resistance in KPC-KP, due to the resulting upregulation of the Pmr lipopolysaccharide modification system. In this work we investigated the status of the mgrB gene in a collection of 66 colistin-resistant nonreplicate clinical strains of KPC-KP isolated from different hospitals in Italy and Greece. Overall, 35 strains (53%) exhibited alterations of the mgrB gene, including insertions of different types of mobile elements (IS5-like, IS1F-like, or ISKpn14), nonsilent point mutations, and small intragenic deletions. Four additional strains had a larger deletion of the mgrB locus, while the remaining 27 strains (41%) did not show mgrB alterations. Transcriptional upregulation of the phoQ and pmrK genes (part of the phoPQ and pmrHFIJKLM operon, respectively) was observed in all strains with mgrB alterations. Complementation experiments with a wild-type mgrB gene restored colistin susceptibility and basal expression levels of phoQ and pmrK genes in strains carrying different types of mgrB alterations. The present results suggest that mgrB alteration can be a common mechanism of colistin resistance among KPC-KP in the clinical setting.

Original languageEnglish
Pages (from-to)5696-5703
Number of pages8
JournalAntimicrobial Agents and Chemotherapy
Volume58
Issue number10
DOIs
Publication statusPublished - Oct 1 2014

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Colistin
Klebsiella pneumoniae
Genes
Up-Regulation
Insertional Mutagenesis
Greece
Gene Silencing
Operon
Point Mutation
Italy
Lipopolysaccharides
Delivery of Health Care
Phenotype
Infection
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Medicine(all)

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Cannatelli, A., Giani, T., D'Andrea, M. M. A., Di Pilato, V., Arena, F., Conte, V., ... COLGRIT Study Group (2014). MgrB inactivation is a common mechanism of colistin resistance in KPC-producing Klebsiella pneumoniae of clinical origin. Antimicrobial Agents and Chemotherapy, 58(10), 5696-5703. https://doi.org/10.1128/AAC.03110-14

MgrB inactivation is a common mechanism of colistin resistance in KPC-producing Klebsiella pneumoniae of clinical origin. / Cannatelli, Antonio; Giani, Tommaso; D'Andrea, Marco M aria; Di Pilato, Vincenzo; Arena, Fabio; Conte, Viola; Tryfinopoulou, Kyriaki; Vatopoulos, Alkiviadis; Rossolini, Gian M aria; COLGRIT Study Group.

In: Antimicrobial Agents and Chemotherapy, Vol. 58, No. 10, 01.10.2014, p. 5696-5703.

Research output: Contribution to journalArticle

Cannatelli, A, Giani, T, D'Andrea, MMA, Di Pilato, V, Arena, F, Conte, V, Tryfinopoulou, K, Vatopoulos, A, Rossolini, GMA & COLGRIT Study Group 2014, 'MgrB inactivation is a common mechanism of colistin resistance in KPC-producing Klebsiella pneumoniae of clinical origin', Antimicrobial Agents and Chemotherapy, vol. 58, no. 10, pp. 5696-5703. https://doi.org/10.1128/AAC.03110-14
Cannatelli, Antonio ; Giani, Tommaso ; D'Andrea, Marco M aria ; Di Pilato, Vincenzo ; Arena, Fabio ; Conte, Viola ; Tryfinopoulou, Kyriaki ; Vatopoulos, Alkiviadis ; Rossolini, Gian M aria ; COLGRIT Study Group. / MgrB inactivation is a common mechanism of colistin resistance in KPC-producing Klebsiella pneumoniae of clinical origin. In: Antimicrobial Agents and Chemotherapy. 2014 ; Vol. 58, No. 10. pp. 5696-5703.
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