PYED-1 Inhibits Biofilm Formation and Disrupts the Preformed Biofilm of <i>Staphylococcus aureus</i>

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 <i>Staphylococcus...

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Main Authors: Adriana Vollaro (Author), Anna Esposito (Author), Eliana Pia Esposito (Author), Raffaele Zarrilli (Author), Annalisa Guaragna (Author), Eliana De Gregorio (Author)
Format: Book
Published: MDPI AG, 2020-05-01T00:00:00Z.
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Summary: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 <i>Staphylococcus aureus</i>, 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 (<i>agrA</i>, <i>RNAIII</i>, <i>hld</i>, <i>psm</i>, and <i>sarA</i>), surface proteins (<i>clfB</i> and <i>fnbB</i>), secreted toxins (<i>hla</i>, <i>hlb,</i> and <i>lukD</i>), and capsular polysaccharides (<i>capC</i>). The expression of genes that encode two main global regulators, <i>sigB</i> and <i>saeR</i>, 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 <i>S. aureus</i>, 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 <i>S. aureus</i> biofilm-associated infections.
Item Description:10.3390/antibiotics9050240
2079-6382