Work

Targeting Autoinducer-2 Quorum Sensing: Novel Inhibitors Attenuate Virulence in Staphylococcus aureus and Pseudomonas aeruginosa

Year: 2026

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide Antibiotic overuse has driven the development of bacterial drug resistance, highlighting the urgent need for new antimicrobial strategies. Quorum sensing, particularly via autoinducer-2 (AI-2) signal molecules, is a bacterial communication system involved in the development of drug resistance. Our recent work identified AI-2 inhibitors that disrupt biofilm formation in Staphylococcus aureus and Pseudomonas aeruginosa . Here, we investigated the efficacy of the three most promising compounds in modulating bacterial virulence. The compounds strongly impaired the bacterial ability to adhere to human epithelial cells. ELISA-based assays and Western blot analyses revealed the efficacy of the compounds in controlling S. aureus virulence by decreasing the levels of bacterial adhesins, α-hemolysin, and protein SpA. In a co-culture with S. aureus, colorimetric assays revealed the compound efficacy in decreasing P. aeruginosa pyocyanin and elastase production in a dose-dependent manner. Importantly, no cytotoxicity was observed both in vitro (A549 cells) and in vivo ( Galleria mellonella model). These results support the potential of our compounds to modulate virulence factor expression consistent with quorum-sensing disruption as promising candidates for the treatment of multidrug-resistant infections.

Source: ACS Omega

DOI: 10.1021/acsomega.5c08721