Vollaro Adriana, Esposito Anna, Esposito Eliana Pia, Zarrilli Raffaele, Guaragna Annalisa, De Gregorio Eliana
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy.
Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy.
Antibiotics (Basel). 2020 May 8;9(5):240. doi: 10.3390/antibiotics9050240.
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 , 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 (, , , , and ), surface proteins ( and ), secreted toxins (, and ), and capsular polysaccharides (). The expression of genes that encode two main global regulators, and , 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 , 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 biofilm-associated infections.
孕二烯-11-羟基-16α,17α-环氧-3,20-二酮-1（PYED-1）是地夫可特的一种杂环皮质类固醇衍生物，对革兰氏阴性菌和革兰氏阳性菌具有广谱抗菌活性。在此，我们研究了PYED-1对[具体细菌名称未给出]生物膜的影响，[该细菌]是基于生物膜的慢性感染的病原体，如骨髓炎、植入式医疗器械感染、牙周炎、慢性伤口感染和心内膜炎。PYED-1以浓度依赖的方式显著减少生物膜形成。此外，它还能够完全去除预先形成的生物膜。对已形成的生物膜进行的转录分析表明，PYED-1下调与群体感应相关的基因（[相关基因名称未给出]）、表面蛋白（[相关基因名称未给出]）、分泌毒素（[相关基因名称未给出]）和荚膜多糖（[相关基因名称未给出]）的表达。在用PYED-1处理后，编码两个主要全局调节因子[相关基因名称未给出]的基因表达也受到显著抑制。总之，PYED-1不仅有效抑制生物膜形成，还能根除预先形成的[具体细菌名称未给出]生物膜，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表达。这些结果表明，PYED-1作为一种有效的抗生物膜剂预防[具体细菌名称未给出]生物膜相关感染可能具有巨大潜力。
