Dalton Piotter

Candida albicans is an opportunistic fungal pathogen capable of large chromosomal rearrangements that confer antifungal drug resistance. One such chromosomal rearrangement results in an isochromosome of chromosome 5L (i(5L)) which confers resistance to azole antifungals, the first line of defense against Candida infections. Azole resistance is promoted due to additional copies of ERG1 and TAC1; which are two genes encoding an azole drug target and a transcription activator of efflux. Recently, we identified a chromosome rearrangement (an inversion) at the centromere of chromosome 5 (CEN5) by PCR. It is unclear if this inversion was an artifact of PCR, a novel feature i(5L), or on the original chromosome. Additionally, the impact of a CEN5 inversion on i(5L) formation and effects on drug resistance are not known. Here we show that isolates lacking i(5L) contained the CEN5 inversion. We selected isolates that had small colony morphology and low fitness in the presence of fluconazole with the expectation that they lacked i(5L) because it confers azole resistance. We examined the karyotypes of isolates subjected to CHEF gel for the presence of i(5L). Interestingly, no chromosome 5 band was present in the karyotype; however, a newly observed band just below chromosome 4 was present. Additionally, a CEN5 inversion was observed by PCR product. The identification of the CEN5 inversion on the parental chromosomes in conjunction with the absence of parental chromosome 5 demonstrates a potential component in i(5L) formation and ultimately drug resistance to azoles in C. albicans. Understanding the mechanisms of acquired antifungal drug resistance is important due to the limited drug classes available for treating Candidemia and the increasing incidence of drug resistant Candida species.