Subinhibitory concentrations of tedizolid induce upregulation of virulence gene transcription in Staphylococcus aureus
DOI:
https://doi.org/10.3855/jidc.20386Keywords:
Staphylococcus aureus, subinhibitory concentration, tedizolid, linezolid, virulence gene, qRT-PCRAbstract
Introduction: Sub-minimal inhibitory concentrations (sub-MICs) of antibiotics can modulate the expression of virulence factors in bacterial pathogens. This study aimed to assess the impacts of sub-MICs of tedizolid on virulence gene expression in Staphylococcus aureus (S. aureus) and compare them with those of linezolid.
Methodology: Two S. aureus strains (N315 and Newman) possessing the selected virulence genes were analyzed. The MICs of tedizolid and linezolid were determined, and sub-MICs for subsequent experiments were selected based on bacterial growth kinetics. Using qRT-PCR, we assessed the expression of 23 virulence genes, including 7 cell wall-anchored (CWA) protein genes, 4 exoenzyme genes, 6 toxin genes, and 6 regulatory genes, before and after exposure to tedizolid and linezolid.
Results: Growth kinetics indicated that 1/8 and 1/4 MICs were optimal for evaluating the influence of drugs on gene expression. The qRT-PCR results revealed that sub-MICs of tedizolid and linezolid primarily enhanced the expression of the studied virulence genes in both strains. In Newman, tedizolid upregulated the expression of more genes encoding CWA proteins, regulators, and toxins than linezolid. In N315, tedizolid stimulated the expression of more toxin-coding genes but fewer regulatory genes compared to linezolid.
Conclusions: Sub-MIC of tedizolid and linezolid could increase the mRNA levels of different types of virulence genes in S. aureus, with strain-dependent variations. These findings provide new insights into the potential role of oxazolidinones in bacterial virulence regulation.
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Copyright (c) 2025 Han Yang, Wen Lin, Chunyan He, Wen Shu, Wenjing Chen, Qingzhong Liu

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Funding data
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National Natural Science Foundation of China
Grant numbers 82172281 -
National Natural Science Foundation of China
Grant numbers 81772247 -
Natural Science Foundation of Shanghai Municipality
Grant numbers 20ZR1444800

