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  • Title: Overexpression of OqxAB and MacAB efflux pumps contributes to eravacycline resistance and heteroresistance in clinical isolates of Klebsiella pneumoniae.
    Author: Zheng JX, Lin ZW, Sun X, Lin WH, Chen Z, Wu Y, Qi GB, Deng QW, Qu D, Yu ZJ.
    Journal: Emerg Microbes Infect; 2018 Aug 01; 7(1):139. PubMed ID: 30068997.
    Abstract:
    This study investigated the characteristics and mechanisms of eravacycline resistance and heteroresistance in clinical Klebsiella pneumoniae isolates. A total of 393 clinical K. pneumoniae isolates were collected and subjected to eravacycline and tigecycline MIC determinations using the agar dilution method. Eravacycline heteroresistance was assessed by a population analysis profile (PAP). The expression levels of efflux pumps and their regulators were determined by quantitative reverse-transcription PCR (qRT-PCR). This study identified 67 eravacycline-nonsusceptible isolates; among the extended-spectrum β-lactamase (ESBL)-positive isolates, eravacycline-nonsusceptible isolates were detected more frequently than tigecycline-nonsusceptible isolates (21.7% vs. 9.4%, p = 0.001). The study sample was observed to include 20 K. pneumoniae isolates with eravacycline heteroresistance. Compared to the reference strain, oqxA or oqxB overexpression was observed in nine eravacycline-nonsusceptible isolates (range, 35.64-309.02-fold) and 13 eravacycline-heteroresistant isolates (8.42-296.34-fold). The overexpression of macA or macB was detected in 12 eravacycline-heteroresistant isolates (3.23-28.35-fold). Overexpression of the efflux pump regulator gene ramA was observed in 11 eravacycline-nonsusceptible isolates (3.33-94.05-fold) and 18 eravacycline-heteroresistant isolates (3.89-571.70-fold). The eravacycline MICs were increased by one-fourfold by overexpression of oqxAB or macAB in three eravacycline-sensitive isolates. In conclusion, the overexpression of OqxAB and MacAB efflux pumps and the transcriptional regulator RamA were suggested to be involved in K. pneumoniae eravacycline resistance and heteroresistance.
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