Open AccessPolymyxin resistance in Klebsiella pneumoniae: multifaceted mechanisms utilized in the presence and absence of the plasmid-encoded phosphoethanolamine transferase gene mcr-1
Author(s) -
Sue C. Nang,
MeiLing Han,
Heidi H. Yu,
Jiping Wang,
Von Vergel L Torres,
Chongshan Dai,
Tony Velkov,
Marina Harper,
Jian Li
Publication year - 2019
Publication title -
the journal of antimicrobial chemotherapy/journal of antimicrobial chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.124
H-Index - 194
eISSN - 1460-2091
pISSN - 0305-7453
DOI - 10.1093/jac/dkz314
Subject(s) - klebsiella pneumoniae , polymyxin , biology , polymyxin b , microbiology and biotechnology , lipid a , antibiotics , bacteria , gene , escherichia coli , biochemistry , genetics
Until plasmid-mediated mcr-1 was discovered, it was believed that polymyxin resistance in Gram-negative bacteria was mainly mediated by the chromosomally-encoded EptA and ArnT, which modify lipid A with phosphoethanolamine (pEtN) and 4-amino-4-deoxy-l-arabinose (l-Ara4N), respectively. This study aimed to construct a markerless mcr-1 deletion mutant in Klebsiella pneumoniae, validate a reliable reference gene for reverse transcription quantitative PCR (RT-qPCR) and investigate the interactions among mcr-1, arnT and eptA, in response to polymyxin treatments using pharmacokinetics/pharmacodynamics (PK/PD).