Abstract
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.
Highlights
Emergence of Candida auris has been described as a global health threat
Carvacrol has been shown to be effective in reduction of the Secreted Aspartyl Proteinase (SAP) gene expression in both susceptible and resistant C. albicans isolates with a higher effect against the resistant isolates12
The Minimum inhibitory concentrations (MIC) of 4 antifungal drugs and 4 phenolic compounds against 26 tested Candida strains are shown in Tables 1 and 2, respectively
Summary
Emergence of Candida auris has been described as a global health threat. C. auris is typically healthcare associated pathogen. The concept of targeting virulence factors has been proposed as an alternative and promising antifungal strategy, since the development of new antifungal drugs is restricted by the limited number of selective drug targets in fungi2,5 Knowledge of these virulence factors in C. auris, which has been reported to be highly resistant to antifungal drugs, will assist in finding new antifungal drug targets and to develop more effective antifungal agents for improved therapeutic regimens. Combination therapy has become an interesting area in developing new therapeutic strategies against fungal infections They can improve the efficacy, overcome drug resistance and reduce the toxicity of antifungal drugs. Several studies have shown that these phenolic compounds possess a synergistic in vitro antifungal activity in combination with antifungal drugs or two essential oils against different Candida isolates, including both susceptible and resistant strains
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