AUTHOR=Zheng Jinxin , Chen Zhong , Lin Zhiwei , Sun Xiang , Bai Bing , Xu Guangjian , Chen Junwen , Yu Zhijian , Qu Di 

TITLE=Radezolid Is More Effective Than Linezolid Against Planktonic Cells and Inhibits Enterococcus faecalis Biofilm Formation

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.00196

DOI=10.3389/fmicb.2020.00196

ISSN=1664-302X

ABSTRACT=<p>The aim of this study was to compare the effects of radezolid and linezolid on planktonic and biofilm cells of <italic>Enterococcus faecalis</italic>. A total of 302 <italic>E. faecalis</italic> clinical isolates were collected, and the minimum inhibitory concentrations (MICs) of radezolid and linezolid were determined by the agar dilution method. Changes in the transcriptome of a high-level, <italic>in vitro</italic>-induced linezolid-resistant isolate were assessed by RNA sequencing and RT-qPCR, and the roles of efflux pump-related genes were confirmed by overexpression analysis. Biofilm biomass was evaluated by crystal violet staining and the adherent cells in the biofilms were quantified according to CFU numbers. The MIC<sub>50</sub>/MIC<sub>90</sub> values of radezolid (0.25/0.50 mg/L) against the 302 <italic>E. faecalis</italic> clinical isolates were eightfold lower than those of linezolid (2/4 mg/L). The radezolid MICs against the high-level linezolid-resistant isolates (linezolid MICs ≥ 64 mg/L) increased to ≥ 4 mg/L with mutations in the four copies of the V domain of the 23S rRNA gene. The mRNA expression level of <italic>OG1RF_12220</italic> (<italic>mdlB2</italic>, multidrug ABC superfamily ATP-binding cassette transporter) increased in the high-level linezolid-resistant isolates, and radezolid and linezolid MICs against the linezolid-sensitive isolate increased with overexpression of <italic>OG1RF_12220</italic>. Radezolid (at 1/4 or 1/8× the MIC) inhibited <italic>E. faecalis</italic> biofilm formation to a greater extent than linezolid, which was primarily achieved through the inhibition of <italic>ahrC</italic>, <italic>esp</italic>, <italic>relA</italic>, and <italic>relQ</italic> transcription in <italic>E. faecalis</italic>. In conclusion, radezolid is more effective than linezolid against planktonic <italic>E. faecalis</italic> cells and inhibits biofilm formation by this bacterium.</p>