Format

Send to

Choose Destination
J Antimicrob Chemother. 2017 Nov 1;72(11):3035-3042. doi: 10.1093/jac/dkx234.

Structural modification of LPS in colistin-resistant, KPC-producing Klebsiella pneumoniae.

Author information

1
Department of Microbial Pathogenesis, School of Dentistry, University of Maryland Baltimore, Baltimore, MD, USA.
2
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
3
Center for Innovative Antimicrobial Therapy, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
4
Institute for Genome Sciences, University of Maryland Baltimore, Baltimore, MD, USA.
5
Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.
6
Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
7
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland Baltimore, Baltimore, MD, USA.
8
Department of Microbiology, Fujita Health University, Aichi, Japan.

Abstract

Background:

Colistin resistance in Klebsiella pneumoniae typically involves inactivation or mutations of chromosomal genes mgrB, pmrAB or phoPQ, but data regarding consequent modifications of LPS are limited.

Objectives:

To examine the sequences of chromosomal loci implicated in colistin resistance and the respective LPS-derived lipid A profiles using 11 pairs of colistin-susceptible and -resistant KPC-producing K. pneumoniae clinical strains.

Methods:

The strains were subjected to high-throughput sequencing with Illumina HiSeq. The mgrB gene was amplified by PCR and sequenced. Lipid profiles were determined using MALDI-TOF MS.

Results:

All patients were treated with colistimethate prior to the isolation of colistin-resistant strains (MIC >2 mg/L). Seven of 11 colistin-resistant strains had deletion or insertional inactivation of mgrB. Three strains, including one with an mgrB deletion, had non-synonymous pmrB mutations associated with colistin resistance. When analysed by MALDI-TOF MS, all colistin-resistant strains generated mass spectra containing ions at m/z 1955 and 1971, consistent with addition of 4-amino-4-deoxy-l-arabinose (Ara4N) to lipid A, whereas only one of the susceptible strains displayed this lipid A phenotype.

Conclusions:

The pathway to colistin resistance in K. pneumoniae primarily involves lipid A modification with Ara4N in clinical settings.

PMID:
28961916
PMCID:
PMC5890713
DOI:
10.1093/jac/dkx234
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center