Antibiofilm activity of truncated Staphylococcus aureus phenol soluble modulin α2 (SaΔ1Δ2PSMα2) against Candida auris in vitro and in an animal model of catheter-associated infection

Candida auris has emerged as a major multidrug-resistant nosocomial pathogen. The organism exhibits a persistent colonising phenotype, and causes recalcitrant infections often strongly linked to biofilm formation. Alternate strategies are urgently needed to combat this yeast and its biofilm-associated phenotype. This work aimed to evaluate the efficacy of select staphylococcal phenol soluble modulins (PSMs), namely, a truncated version of Staphylococcus aureus PSM alpha 2 shortened by two amino acids at the N-terminal (Sa Delta 1 Delta 2PSM alpha 2) and Staphylococcus epidermidis PSM delta against C. auris in vitro and in vivo. The antifungal and antibiofilm activity was tested by broth microdilution and XTT dye reduction assay. Combination effect with antifungal drugs was determined by fractional inhibitory concentration test. The efficacy of combination therapy using Sa Delta 1 Delta 2PSM alpha 2 with amphotericin B or caspofungin was evaluated in murine model of C. auris catheter-associated infection. Based on antifungal activity, antibiofilm activity and cytotoxicity data, Sa Delta 1 Delta 2PSM alpha 2 exhibited promising activity against C. auris biofilms. Nearly 50 % inhibition in biofilm formation was noted with 0.5-2 mu M of the peptide against multiple clinical and C. auris colonizing isolates. It was synergistic with amphotericin B (Sigma FIC = 0.281) and caspofungin (Sigma FIC = 0.047) in vitro, and improved the activity of voriconazole in voriconazole-resistant C. auris. Combination therapy using amphotericin B or caspofungin (1 mu g/ml) with Sa Delta 1 Delta 2PSM alpha 2 resulted in 99.5 % reduction in C. auris biofilm in murine model, even when the peptide was used at a concentration that was neither fungicidal nor antibiofilm (0.125 mu M; approximate to 0.26 mu g/ml). The study provides insight into the potential utility of Sa Delta 1 Delta 2PSM alpha 2-antifungal drug combination against C. auris biofilm-associated infections.