Drug Sensitivity and Resistance Mechanism in Aspergillus Section Nigri Strains from Japan

Aspergillus niger and its related species, known asAspergillus sectionNigri , are ubiquitously distributed across the globe and are often isolated from clinical specimens. In Japan,Aspergillus sectionNigri is second most often isolated from clinical specimens followingAspergillus fumigatus . We determined the species ofAspergillus sectionNigri isolated in Japan by DNA sequencing of partial β-tubulin genes and investigated drug susceptibility by the CLSI M38-A2 method. The collection contained 20Aspergillus niger , 59Aspergillus welwitschiae , and 39Aspergillus tubingensis strains. Drug susceptibility testing revealed 30 to 55% ofA. niger , 6.8 to 18.6% ofA. welwitschiae , and 79.5 to 89.7% ofA. tubingensis isolates to be less susceptible (so-called resistant) to itraconazole (ITC) and/or voriconazole (VRC) according to the epidemiologic cutoff values (ECVs) proposed forA. niger previously. MIC distributions of ITC or VRC showed no remarkable differences between clinical and environmental isolates. When thecyp51A sequences were compared between susceptible and resistant strains, 18 amino acid mutations were specific for resistant isolates ofA. niger andA. tubingensis ; however, none of them were confirmed to be associated with azole resistance. Three nonrelatedA. welwitschiae isolates possessed a partial deletion incyp51A , likely attributable to being more susceptible to azoles than other isolates. One of five ITC-resistantA. tubingensis isolates showed higher expression ofcyp51A than did susceptible strains. Our results show thatcyp51A point mutations may have no association with azole resistance but that in some cases the overexpression ofcyp51A may lead to the azole resistance in these species.