Characterization of Defensin-like Protein 1 for Its Anti-Biofilm and Anti-Virulence Properties for the Development of Novel Antifungal Drug against Candida auris.

ABSTRACT

Candida auris has emerged as a pan-resistant pathogenic yeast among immunocompromised patients worldwide. As this pathogen is involved in biofilm-associated infections with serious medical manifestations due to the collective expression of pathogenic attributes and factors associated with drug resistance, successful treatment becomes a major concern. In the present study, we investigated the candidicidal activity of a plant defensin peptide named defensin-like protein 1 (D-lp1) against twenty-five clinical strains of C. auris. Furthermore, following the standard protocols, the D-lp1 was analyzed for its anti-biofilm and anti-virulence properties. The impact of these peptides on membrane integrity was also evaluated. For cytotoxicity determination, a hemolytic assay was conducted using horse blood. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values ranged from 0.047-0.78 mg/mL and 0.095-1.56 mg/mL, respectively. D-lp1 at sub-inhibitory concentrations potentially abrogated both biofilm formation and 24-h mature biofilms. Similarly, the peptide severely impacted virulence attributes in the clinical strain of C. auris. For the insight mechanism, D-lp1 displayed a strong impact on the cell membrane integrity of the test pathogen. It is important to note that D-lp1 at sub-inhibitory concentrations displayed minimal hemolytic activity against horse blood cells. Therefore, it is highly useful to correlate the anti-Candida property of D-lp1 along with anti-biofilm and anti-virulent properties against C. auris, with the aim of discovering an alternative strategy for combating serious biofilm-associated infections caused by C. auris.