Inhibition of Candida albicans virulence factor by cyclic dipeptides derived from Aeromonas veronii V03

Candida albicans is the most common human fungal pathogen with high mortality rates and limited antifungal treatments. Inhibition of C. albicans pathogenesis by targeting virulence factors provides a promising strategy for the development of novel antifungal drugs and overcoming drug resistance. In this study, four structurally different cyclic dipeptides (or diketopiperazine(DKP) were isolated and identified as cyclo(L-Pro-L-Leu), cyclo(L-Pro-L-Val), cyclo(D-Pro-L-Phe), and cyclo(L-Pro-D-Tyr) from Aeromonas veronii V03 and their antimicrobial potentials were evaluated. Results revealed that identified DKPs exhibited antibacterial activity against bacterial pathogens, such as Staphylococcus aureus, Proteus mirabilis , Pseudomonas aeruginosa, and Aeromonas hydrophila . Importantly, cyclo(D-Pro-L-Phe) lacking hydroxyl groups showed potent inhibitory effects against C. albicans and non-albicans species with low concentrations. Moreover, identified DKPs inhibited the virulence traits of C. albicans, including yeast-to-hyphae transition, secreted hydrolases (aspartic proteases and phospholipase) and biofilm formation in a dose-dependent manner. Collectively, our findings suggest that cyclic dipeptides from DKPs derived from A. veronii V03 could potentially be developed as antivirulence agents against C. albicans infection.