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Molecules 2018, 23(12), 3195;

Intracellular Accumulation of Linezolid and Florfenicol in OptrA-Producing Enterococcus faecalis and Staphylococcus aureus

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
Institute of Microbiology and Epizootics, Centre for Infection Medicine, Department of Veterinary Medicine, Freie Universität Berlin, 14163 Berlin, Germany
Author to whom correspondence should be addressed.
Received: 20 November 2018 / Revised: 30 November 2018 / Accepted: 1 December 2018 / Published: 4 December 2018
(This article belongs to the Special Issue Biological Sample Analysis by Liquid Chromatography)
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The optrA gene, which confers transferable resistance to oxazolidinones and phenicols, is defined as an ATP-binding cassette (ABC) transporter but lacks transmembrane domains. The resistance mechanism of optrA and whether it involves antibiotic efflux or ribosomal protection remain unclear. In this study, we determined the MIC values of all bacterial strains by broth microdilution, and used ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry to quantitatively determine the intracellular concentrations of linezolid and florfenicol in Enterococcus faecalis and Staphylococcus aureus. Linezolid and florfenicol both accumulated in susceptible strains and optrA-carrying strains of E. faecalis and S. aureus. No significant differences were observed in the patterns of drug accumulation among E. faecalis JH2-2, E. faecalis JH2-2/pAM401, and E. faecalis JH2-2/pAM401+optrA, but also among S. aureus RN4220, S. aureus RN4220/pAM401, and S. aureus RN4220/pAM401+optrA. ANOVA scores also suggested similar accumulation conditions of the two target compounds in susceptible strains and optrA-carrying strains. Based on our findings, the mechanism of optrA-mediated resistance to oxazolidinones and phenicols obviously does not involve active efflux and the OptrA protein does not confer resistance via efflux like other ABC transporters. View Full-Text
Keywords: linezolid; florfenicol; Enterococcus; Staphylococcus; active efflux; ABC transporter linezolid; florfenicol; Enterococcus; Staphylococcus; active efflux; ABC transporter

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Wang, Y.; Li, X.; Wang, Y.; Schwarz, S.; Shen, J.; Xia, X. Intracellular Accumulation of Linezolid and Florfenicol in OptrA-Producing Enterococcus faecalis and Staphylococcus aureus. Molecules 2018, 23, 3195.

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