PYED-1 Inhibits Biofilm Formation and Disrupts the Preformed Biofilm of Staphylococcus aureus.

Adriana Vollaro,Eliana De Gregorio,Anna Esposito,Annalisa Guaragna,Raffaele Zarrilli,Eliana Pia Esposito

doi:10.3390/antibiotics9050240

Adriana Vollaro, Eliana De Gregorio + Show 4 more

Open Access

https://doi.org/10.3390/antibiotics9050240

Copy DOI

Abstract

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.

Highlights

One of the bacterial growth modes is the development of biofilms, which may be considered a basic survival strategy in hostile environments [1]
Effect of PYED-1 on S. aureus Biofilm Formation has the ability to produce a biofilm, which protects it from the action of antibacterial
S. aureus has the ability to produce a biofilm, which protects it from the action of antibacterial of disease progression, and elimination this may pathogen from the targetforsite infection [14]

Summary

Introduction

One of the bacterial growth modes is the development of biofilms, which may be considered a basic survival strategy in hostile environments [1]. Biofilms are sessile communities of bacterial cells, attached to each other and/or to surfaces, embedded in a self-produced matrix of extracellular polymeric substances (EPS) [2]. Biofilm formation plays a crucial role in bacterial infection and antimicrobial resistance, because biofilm-embedded bacteria are more resistant to common antimicrobial agents and host defense systems than bacteria in the planktonic state [3]. Increasing evidence demonstrates that cells in biofilms on a biotic or abiotic surface are 1000-fold more resistant to conventional drugs than planktonic cells [4,5]. Biofilms become difficult to eradicate, leading to chronic and persistent infections [6]. Staphylococcus aureus is the major Gram-positive pathogen which causes biofilm-associated infections, because of its ability to form biofilms on a wide range of surfaces [7,8]

Objectives

Methods

Results

Conclusion