Pregnadiene-11-hydroxy-16α,17α-epoxy-3,20-dione-1 (PYED-1), a heterocyclic corticosteroid derivative of deflazacort, exhibits broad-spectrum antibacterial activity against Gram-negative and Gram-positive bacteria. Here, we investigated the effect of PYED-1 on the biofilms of Staphylococcus aureus, an etiological agent of biofilm-based chronic infections such as osteomyelitis, indwelling medical device infections, periodontitis, chronic wound infections, and endocarditis. PYED-1 caused a strong reduction in biofilm formation in a concentration dependent manner. Furthermore, it was also able to completely remove the preformed biofilm. Transcriptional analysis performed on the established biofilm revealed that PYED-1 downregulates the expression of genes related to quorum sensing (agrA, RNAIII, hld, psm, and sarA), surface proteins (clfB and fnbB), secreted toxins (hla, hlb, and lukD), and capsular polysaccharides (capC). The expression of genes that encode two main global regulators, sigB and saeR, was also significantly inhibited after treatment with PYED-1. In conclusion, PYED-1 not only effectively inhibited biofilm formation, but also eradicated preformed biofilms of S. aureus, modulating the expression of genes related to quorum sensing, surface and secreted proteins, and capsular polysaccharides. These results indicated that PYED-1 may have great potential as an effective antibiofilm agent to prevent S. aureus biofilm-associated infections.

中文翻译：

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PYED-1抑制生物膜形成并破坏金黄色葡萄球菌的预先形成的生物膜。

Prefladicort的杂环皮质类固醇衍生物Pregnadiene-11-hydroxy-16α，17α-epoxy-3,20-dione-1（PYED-1）对革兰氏阴性和革兰氏阳性细菌表现出广谱抗菌活性。在这里，我们研究了PYED-1对金黄色葡萄球菌生物膜的影响，金黄色葡萄球菌是基于生物膜的慢性感染（如骨髓炎，留置性医疗器械感染，牙周炎，慢性伤口感染和心内膜炎）的病原体。PYED-1以浓度依赖的方式大大降低了生物膜的形成。此外，它还能够完全去除预制的生物膜。对已建立的生物膜进行的转录分析表明，PYED-1下调了与群体感应相关的基因（agrA，RNAIII，hld，psm和sarA），表面蛋白（clfB和fnbB）的表达，分泌的毒素（hla，hlb和lukD）和荚膜多糖（capC）。用PYED-1处理后，编码两个主要的全局调节子sigB和saeR的基因的表达也被显着抑制。总之，PYED-1不仅可以有效抑制生物膜的形成，而且可以根除金黄色葡萄球菌的预先形成的生物膜，从而调节与群体感应，表面和分泌蛋白以及荚膜多糖相关的基因的表达。这些结果表明，PYED-1作为预防金黄色葡萄球菌生物膜相关感染的有效抗生物膜剂可能具有巨大潜力。PYED-1不仅有效抑制生物膜的形成，而且还消除了金黄色葡萄球菌的预先形成的生物膜，从而调节了与群体感应，表面和分泌蛋白以及荚膜多糖相关的基因的表达。这些结果表明，PYED-1作为预防金黄色葡萄球菌生物膜相关感染的有效抗生物膜剂可能具有巨大潜力。PYED-1不仅有效抑制生物膜的形成，而且还消除了金黄色葡萄球菌的预先形成的生物膜，从而调节了与群体感应，表面和分泌蛋白以及荚膜多糖相关的基因的表达。这些结果表明，PYED-1作为预防金黄色葡萄球菌生物膜相关感染的有效抗生物膜剂可能具有巨大潜力。