Polymyxin resistance in Klebsiella pneumoniae: multifaceted mechanisms utilized in the presence and absence of the plasmid-encoded phosphoethanolamine transferase gene mcr-1
Sue C Nang, Mei-Ling Han, Heidi H Yu, Jiping Wang, Von Vergel L Torres, Chongshan Dai, Tony Velkov, Marina Harper, Jian Li
Journal of Antimicrobial Chemotherapy | OXFORD UNIV PRESS | Published : 2019
OBJECTIVES: 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). METHODS: An isogenic markerless mcr-1 deletion mutant (II-503Δmcr-1) was gen..View full abstract
Awarded by NIAID/NIH
Awarded by National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIAID)
The study was supported by a research grant from the NIAID/NIH (R01 AI132154). J. L. and T. V. are also funded by National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIAID) (R01 AI111965). J. L. is an Australian National Health and Medical Research Council (NHMRC) Principal Research Fellow and T. V. is an Australian NHMRC Career Development Research Fellow.