AUTHOR=Wang Cong , Xiong Yanpeng , Bao Chai , Wei Ying , Wen Zewen , Cao Xinyi , Yu Zhijian , Deng Xiangbing , Li Guiqiu , Deng Qiwen 

TITLE=Antibacterial and anti-biofilm activity of radezolid against Staphylococcus aureus clinical isolates from China

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1131178

DOI=10.3389/fmicb.2023.1131178

ISSN=1664-302X

ABSTRACT=<p>Although the potent antibacterial ability of radezolid against <italic>Staphylococcus aureus</italic> has been widely reported worldwide, its antibacterial and anti-biofilm activity against the <italic>S. aureus</italic> clinical isolates from China remains elusive. In this study, the minimum inhibitory concentration (MIC) of radezolid was determined in <italic>S. aureus</italic> clinical isolates from China using the agar dilution method, and the relationship between radezolid susceptibility and ST distribution was also investigated. The anti-biofilm activity of radezolid against <italic>S. aureus</italic> was determined by a crystal violet assay and compared with that of linezolid and contezolid. The quantitative proteomics of <italic>S. aureus</italic> treated with radezolid was analyzed, and the genetic mutations in radezolid-induced resistant <italic>S. aureus</italic> were determined by whole-genome sequencing. The dynamic changes in transcriptional expression levels of several biofilm-related genes were analyzed by quantitative RT-PCR. Our data showed that radezolid MIC ranged from ≤0.125 to 0.5 mg/L, which was almost 1/4 × MIC of linezolid against <italic>S. aureus</italic>, indicating the greater antibacterial activity of radezolid than linezolid. The <italic>S. aureus</italic> clinical isolates with radezolid MICs of 0.5 mg/L were most widely distributed in ST239 of MRSA and ST7 of MSSA. Moreover, the more robust anti-biofilm activity of radezolid with subinhibitory concentrations (1/8 × MIC and 1/16 × MIC) was demonstrated against <italic>S. aureus</italic> when compared with that of contezolid and linezolid. Genetic mutations were found in <italic>glmS</italic>, 23S rRNA, and DUF1542 domain-containing protein in radezolid-induced resistant <italic>S. aureus</italic> selected by <italic>in vitro</italic> induction of drug exposure. Quantitative proteomic analysis of <italic>S. aureus</italic> indicated that the global expression of some biofilm-related and virulence-related proteins was downregulated. Quantitative RT-PCR further confirmed that the expressions of some downregulated biofilm-related proteins, including <italic>sdrD, carA</italic>, <italic>sraP</italic>, <italic>hlgC</italic>, <italic>sasG</italic>, <italic>spa</italic>, <italic>sspP</italic>, <italic>fnbA</italic>, and <italic>oatA</italic>, were decreased after 12 h and 24 h of exposure to radezolid. Conclusively, radezolid shows robust antibacterial and anti-biofilm activity against <italic>S. aureus</italic> clinical isolates from China when compared with contezolid and linezolid.</p>