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


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.

SUBMITTER: Leung LM 

PROVIDER: S-EPMC5890713 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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

Leung Lisa M LM   Cooper Vaughn S VS   Rasko David A DA   Guo Qinglan Q   Pacey Marissa P MP   McElheny Christi L CL   Mettus Roberta T RT   Yoon Sung Hwan SH   Goodlett David R DR   Ernst Robert K RK   Doi Yohei Y  

The Journal of antimicrobial chemotherapy 20171101 11


<h4>Background</h4>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.<h4>Objectives</h4>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.<h4>Methods</h4>The strains were subject  ...[more]

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