Epidemiological Characteristics of Clinical Aspergillus Section Nigri and Mutations in cyp51A Gene

Aspergillus section Nigri is distributed ubiquitously in nature and is reported to be the third most clinically significant species of the Aspergillus genus. In this study, we surveyed Aspergillus section Nigri isolates from Zhongshan Hospital, Fudan University, Shanghai, China, from 2019 to 2023. We determined the species distribution of section Nigri isolates by partial β-tubulin gene sequencing. We characterized the antifungal susceptibility profiles of these isolates to medical azoles (itraconazole, voriconazole, posaconazole, and isavuconazole) using the SensititreTM custom-designed broth microdilution system. The cyp51A sequences were compared between azole-resistant and azole-susceptible strains in order to determine the potential antifungal resistance mechanism. A total of 54 Aspergillus section Nigri isolates were obtained. A. tubingensis (50.0%) and A. niger (46.3%) were the most prevalent species. Two isolates of A. welwitschiae were identified. Resistance to Itraconazole, voriconazole, and isavuconazole was found in 26%, 33.3%, and 33.3% of A. tubingensis isolates, respectively. All A. niger and A. welwitschiae isolates were sensitive to these azoles. Three amino acid mutations were found in azole-resistant A. tubingensis isolates, namely Y119F, Y119H, and T321A. Results from this study provide us with an understanding of species distribution and antifungal susceptibility profiles of clinical Aspergillus section Nigri isolates in Eastern China. It highlights the importance of accurate species identification and antifungal susceptibility testing. Our results also suggest that the novel Y119F substitution is potentially a key player in azole resistance.