Antifungal Drug Susceptibility Profiles and Molecular Mechanisms of Azole Resistance of Candida tropicalis Isolated from a Tertiary Teaching Hospital in Xuzhou

Jingfang Sun,1,* Xinyi Liang,2,* Yan Chen,3 Yi Guo,4 Yinhai Xu,1 Haiquan Kang1 1Department of Laboratory Medicine, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, People’s Republic of China; 2College of Medical Technology, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 3Department of Laboratory Medicine, Chongqing General Hospital, Chongqing, 401147, People’s Republic of China; 4Department of Laboratory Medicine, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yinhai Xu, Department of Laboratory Medicine, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China, Email [email protected] Haiquan Kang, Department of Laboratory Medicine, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China, Email [email protected]: Candida tropicalis (C. tropicalis), a WHO high-priority pathogen, causes invasive multi-system infections and is associated with rising azole resistance. Given that its resistance patterns exhibit significant geographical variation, conducting regional and institutional resistance monitoring is of critical importance. Currently, there is limited research on drug resistance testing of C. tropicalis in Xuzhou, China. Here, we aimed to analyze the strain distribution characteristics and in vitro drug susceptibility profiles of C. tropicalis in a tertiary hospital in Xuzhou, and to explore the mechanisms of azole resistance.Methods: Antifungal susceptibility testing was performed on 86 clinical isolates of C. tropicalis using Sensititre Yeast one YO10 panels to determine the minimum inhibitory concentrations (MICs). Quantitative Real-time PCR (qRT-PCR) was employed to measure the expression levels of the CDR1, MDR1, and ERG11 genes. Sanger sequencing was conducted to analyze mutations at the ERG11.Results: The 86 clinical isolates were predominantly isolated from male patients, with the highest distribution observed in intensive care unit (ICU) departments. Primary specimen sources included urine, bronchoalveolar lavage fluid, and blood. Overall, 25.6% of isolates were resistant to fluconazole, with 81.8% of these showing cross-resistance to voriconazole. The expression level of ERG11 was significantly upregulated in fluconazole-resistant strains compared to susceptible and susceptible-dose dependent (SDD) strains (P < 0.05). In contrast, no significant differences in the expression of CDR1 or MDR1 were observed among the groups. None of the assessed mutations (T374C (V125A), A395T (Y132F), C461T (S154F), T769C (Y257H), G1390A (G464S)) were found in susceptible or SDD strains. In contrast, among fluconazole-resistant isolates, the A395T and C461T mutations were present in 63.6% (14/22) and 68.2% (15/22) of strains, respectively, whereas the T374C, T769C, and G1390A mutations were absent.Conclusion: Overexpression and point mutations of ERG11 contribute to azole resistance in C. tropical in Xuzhou.Keywords: C. tropicalis, azole resistance, ERG11 genes