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 modificationsystem. In this work we investigated the status of the mgrB gene in a collection of 66 colistin-resistant nonreplicateclinical strains of KPC-KP isolated from different hospitals in Italy and Greece. Overall, 35 strains (53%) exhibited alterations ofthe mgrB gene, including insertions of different types of mobile elements (IS5-like, IS1f-like, or IS Kpnl4), 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.

Cannatelli, A., Giani, T., D'Andrea, M.m., Pilato, V.d., Arena, F., Conte, V., et al. (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 [10.1128/AAC.03110-14].

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

D'Andrea M. M.;
2014-01-01

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 modificationsystem. In this work we investigated the status of the mgrB gene in a collection of 66 colistin-resistant nonreplicateclinical strains of KPC-KP isolated from different hospitals in Italy and Greece. Overall, 35 strains (53%) exhibited alterations ofthe mgrB gene, including insertions of different types of mobile elements (IS5-like, IS1f-like, or IS Kpnl4), 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.
2014
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA
Settore BIO/19 - MICROBIOLOGIA GENERALE
English
Con Impact Factor ISI
http://aac.asm.org/content/58/10/5696.full.pdf+html
Cannatelli, A., Giani, T., D'Andrea, M.m., Pilato, V.d., Arena, F., Conte, V., et al. (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 [10.1128/AAC.03110-14].
Cannatelli, A; Giani, T; D'Andrea, Mm; Pilato, Vd; Arena, F; Conte, V; Tryfinopoulou, K; Vatopoulos, A; Rossolini, Gm
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/226239
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 260
  • ???jsp.display-item.citation.isi??? 258
social impact