Anti-virulence and anti-efflux pump activity of synthetic defensins and histatin in Candida auris.

Novel antifungal therapies are needed to combat multidrug-resistant Candida auris, a pathogen with significant virulence and efflux pump activity. Building on our previous work demonstrating the fungicidal activity of selected antimicrobial peptides (AMPs) towards C. auris, this study investigates their effects against virulence factors and efflux pump. We evaluated the impact of human β-Defensin-3 (hBD-3), Human neutrophil peptide-1 (HNP-1) and human salivary histatin 5 (His 5) on C. auris virulence and resistance, using two clinical isolates. Their effect on adhesion and proteinase activity was studied using adherence assay and BSA plates, respectively. Their impact on biofilm formation and mature biofilm was studied using the MTT reduction test and further visualized using Confocal laser scanning microscope. Intracellular accumulation and external efflux of rhodamine-6-G was studied to establish their action on efflux pump activity. In addition, their effect on the expression of related genes was studied using RT-qPCR. At sub-minimum inhibitory concentrations (sub-MICs) and minimum inhibitory concentrations (MICs), all three test AMPs significantly reduced both adherence and proteinase activity. All the test peptides substantially inhibited the metabolic activity and decreased the density of growing and mature biofilms. Moreover, the tested peptides effectively obstructed efflux pumps and downregulated the genes linked to virulence and efflux pumps, including CDR1, CDR2, MDR1, SAP3, SNQ2, PGA26, PGA7 and PGA52. Finally, the safety of these peptides was verified by a haemolytic test. The finding of this study demonstrated the anti-virulence and anti-efflux pump properties of the tested AMPs. Therefore, these peptides can be a potentially effective alternative for managing infections caused by C. auris.