Azole Resistance and ERG11 Mutation in Clinical Isolates of Candida tropicalis

Abstract

We investigated the molecular mechanisms underlying azole resistance in seven <i>Candida tropicalis</i> isolates that caused candidemia and candiduria in Paraná, Brazil (2016-2022). Biofilm production, antifungal susceptibility testing, multilocus sequence typing, amplification and sequencing of <i>ERG11</i>, and quantification of <i>ERG11</i>, <i>MDR1</i>, and <i>CDR1</i> expression levels were performed. Notably, five isolates (71.4%) were from urine samples and two (28.6%) were from blood samples. All strains were biofilm producers, with levels ranging from moderate to strong. The minimum inhibitory concentration (MIC) values ranged from 8->64 mg/L for fluconazole and 0.25-1 mg/L for voriconazole. All isolates had mutations in <i>ERG11</i>; Y132F and Y257N were predominant (71.4%), followed by Y132F and S154F (14.3%) and Y257H (14.3%). No differences in <i>ERG11</i> expression were found between the susceptible and resistant groups, but <i>MDR1</i> and <i>CDR1</i> were more highly expressed in the susceptible isolates. All the isolates contained previously unassigned diploid sequence types. The emergence of <i>C. tropicalis</i> azole resistance has been previously described in Brazil; however, the presence of resistant isolates in urine highlights the need for surveillance resistant strains in both urinary and invasive contexts. In our study mutations in <i>ERG11</i> were the main resistance mechanism identified in <i>C. tropicalis</i>.