Aspergillus latus: A cryptic causative agent of aspergillosis emerging in Japan.

Allodiploid hybrid species, Aspergillus latus, belonging to section Nidulantes, is a hybrid of A. spinulosporus and an unknown species closely related to A. quadrilineatus and A. sublatus. This hybrid has often been misidentified as the species in section Nidulantes, such as A. nidulans, A. spinulosporus, A. sublatus, or other cryptic species. Aspergillus latus has not been reported in Japan as well as Asia so far. In this study, we screened 23 clinical strains identified as A. spinulosporus isolated in Japan from 2012 to 2023 and found seven A. latus strains. To characterize the A. latus strains, we conducted comprehensive phenotyping including morphological observation, whole genome sequences, and phylogenetic analysis based on calmodulin (CaM) gene. In addition, we conducted antifungal susceptibility testing for A. latus strains. As a result, the morphological characters of A. latus were more similar to those of A. spinulosporus compared to A. sublatus. However, the ascospore of A. latus differed from that of A. spinulosporus. Phylogenetic analysis revealed that different CaM alleles from the same isolate clustered separately with A. spinulosporus and A. sublatus, consistent with its hybrid origin. Furthermore, A. latus strains showed reduced susceptibility to caspofungin and amphotericin B compared to A. spinulosporus, while they were susceptible to azoles. Our results suggest that A. latus has been a causative pathogen of aspergillosis in Japan since 2013.