Identification and characterization of PTR or POT and DHA1 transporters in Candida auris

Abstract

Among the different mycotic infections caused by opportunistic fungi, candidiasis an infection caused by Candida species, is considered the most threatening due to severity of the disease and higher occurrence worldwide (Kumar et al., 2020). The rapid emergence of multidrug resistant strains of Candida auris in clinical settings across all continents within a short span of time has necessitated the need for exploring other options for the treatment of C. auris infections. A recent elaborate study on clinical isolates of C. auris highlighted the possibility of utilizing the peptide permeases for the same, wherein increased transcripts of a di-/tripeptide permease PTR22, belonging to the PTR/POT family was observed in a highly multidrug resistant strain (Shahi et al., 2022). The same gene was also observed to be induced under the influence of an azole antifungal, voriconazole in another clinical isolate. These two observations along with certain findings in case of Candida species wherein, such proteins have been exploited for the delivery of antifungal peptides (Liu et al., 2018; Schielmann et al., 2017; Skwarecki et al., 2018) provided the impetus for this study where it is planned to characterize the diand tripeptide transporters of C. auris to pave way for their utilization as antifungal delivery agents. In Candida auris besides target alterations, efflux mechanisms contribute maximally to antifungal resistance. Since amongst the efflux transporters, the members of the drug/H+ antiporter family 1 (DHA1) strongly contribute towards xenobiotic efflux, we aimed to provide a complete landscape of the DHA1 transporters encoded in the genome of C. auris. Furthermore, by constructing and analyzing deletion and overexpression mutants of one DHA1 transporter gene CauMDR1, it is also planned to map its substrates. newline