Sub-Therapeutic Concentrations of Hexetidine Induce Virulence Gene Expression in Candida albicans

Intraoral concentrations of antimicrobial agents such as hexetidine (HEX) using alternative antimycotics fluctuate significantly due to the dynamics in the oral cavity, which can affect both the virulence capacity and the outcome of antimycotic therapy in the management of denture stomatitis-associated oral candidiasis.

This study was carried out to evaluate the impact of different sub-therapeutic HEX concentrations (1/100, 1/200) for different times (0.5, 2, 24, 48 h) on the expression levels of the virulence (hwp1, plb1, plb2, sap4, sap5, sap6) and drug-resistance (cdr1, cdr2, mdr1, erg11) genes of Candida albicans SC5314. Total RNA was extracted immediately after antimicrobial exposure. The qRT-PCR data were performed using the comparative 2^-ΔΔCT method to calculate the relative expression of the target genes after treatment to HEX concentrations, standardized to the actin housekeeping gene.

Expression levels of the hwp1 and plb1 genes decrease after exposure to HEX to higher concentrations at 0.5 h, while the expression level of the plb2 gene increases. Only the expression of the erg11 gene showed a significant decrease within the resistance genes at 0.5 h. Sap5, plb2, and mdr1 are overexpressed at 48 h. Sub-therapeutic levels of HEX affect the virulence and drug-resistance genes of C. albicans.

These results give an idea of future strategies for developing and using HEX as an adjunctive therapy for oral candidiasis. The innovation and clinical relevance of our research lie in its exploration of how low doses of HEX influence gene expression over varying time periods, potentially paving the way for alternative therapeutic strategies.