Investigation of the distribution of species, detection of the susceptibility to azoles, and molecular mechanisms of resistance to azoles in candida parapsilosis complex fungemia isolates in hacettepe university clinical mycology laboratory, Hacettepe University Faculty of Medicine

Candida parapsilosis complex is important in fungemia, consisting of Candida parapsilosis sensu stricto, Candida orthopsilosis and Candida metapsilosis species, which cannot be separated biologically and phenotypically and have different resistance profiles and prevalence. Susceptibility to azoles is decreasing in this species. In this study, it was aimed to determine the species distribution in C.parapsilosis complex fungemia isolates and to reveal molecular mechanisms causing decreased susceptibility to azoles. Species-level identification was determined by the secondary alcohol dehydrogenase (SADH) gene Restriction Fragment Lenght Polymorphism (RFLP) method in these isolates obtained from peripheral and catheter-drawn blood samples in 1997-2017 at Hacettepe University Hospitals Mycology Laboratory. The minimum inhibitory concentration (MIC) values of fluconazole, voriconazole and posaconazole were determined and interpreted according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). DNA sequences of ERG11 and MRR1 genes were analyzed for molecular mechanisms of resistance. In 181 isolates per patient, 180 were C.parapsilosis sensu stricto, and one was C. orthopsilosis. The fluconazole resistance rate was 13.2% (24/181). For the ERG11 gene, 37 non-susceptible isolates of 53 isolates had A395T (Y132F) mutation and six isolates had G1372A (G458S) mutation. In addition, G1261A (D421N) mutation, which was not previously reported, was found in two isolates. The silent T591C (I197I) mutation was demonstrated in 52 of 53 isolates including susceptible and resistant isolates. In the MRR1 gene, G1214A (R405K) mutation was detected in 29 isolates and G2779T (G927D) mutation was found in four isolates. The resistance to azoles increased over the years and the molecular mechanisms causing the resistance were compatible with the literature. The relationship of G1261A (D421N) mutation, which has not been previously reported, with azole resistance should be demonstrated with further studies.