Improved efficacy of antifungal drugs in combination with monoterpene phenols against Candida auris

Emergence of Candida auris has been described as a global health threat due to its ability to cause invasive infections with high mortality rate and multidrug resistance. Novel drugs and therapies are required to target this organism and its pathogenicity. Anti-virulence approach and combination therapy have been proposed as alternatives in recent years. This study evaluated the virulence factors in C. auris, combination antifungal activity of phenolic compounds with antifungal drugs and determined effect of the most active compound on positive pathogenicity markers of C. auris. Antifungal susceptibility profile of 25 clinical isolates of C. auris against antifungal agents as well as against phenolic compounds was obtained using CLSI guidelines. Combination of the most active phenolic compound with antifungal drugs was determined. Effect of carvacrol on the virulence factors was also studied. Carvacrol was the most active phenol with median MIC of 125 µg/ml and its combination with fluconazole, amphotericin B, nystatin and caspofungin resulted synergistic and additive effects in 68%, 64%, 96% and 28%, respectively. Combination also reduced the MIC values of the drugs. All test strains showed adherence ability to epithelial cells and 96% of strains produced proteinase. None of the strains produced hyphae and phospholipase. At low concentrations, carvacrol significantly inhibited the adherence ability and proteinase production (both p < 0.01). Carvacrol has antifungal and anti-virulence activity against C. auris. It also showed an enhanced antifungal activity in combination with antifungal agents. Therefore it has potential to be developed into a novel antifungal agent.