Whole-Genome Sequencing of Newly Emerged Fungal Pathogen and Its Azole Resistance Gene Prediction.

is an important newly recorded species in the complex and its resistance to azole drugs and the high mortality rate of infected individuals have emerged as problems. Comprehensive understanding of the is limited due to lack of genome-wide fine mapping data. The aim of this study was to investigate the signature at the molecular level, analyze the genome-wide profile of this strain, and predict its possible genes that execute azole resistance. In this study, a whole-genome sequencing of a clinically isolated strain (named PWCAL1) was studied by PacBio Sequel sequencing platform. Azole resistance genes were predicted based on whole-genome sequencing data analysis, gene function annotation, comparative genomic analysis, and BLASTP alignment using the Mycology Antifungal Resistance Database to comprehensively understanding the genome-wide features, pathogenicity, and resistance mechanisms of . The results of whole-genome sequencing demonstrated that the total length of PWCAL1 genome was 31255105 bp, the GC content was 49.24%, and 6883 coding genes were predicted. A total of 4565, 1824, and 6405 genes were annotated in the Gene Ontology, Clusters of Orthologous Groups, and Kyoto Encyclopedia of Genes and Genomes databases, respectively. In the Pathogen Host Interactions Database and the Database of Fungal Virulence Factors, 949 and 259 interacting virulence factors were identified, respectively, with the main virulence factor-mutant virulence phenotype, being enriched in reduced virulence. Comparative genomic analysis showed that there were 5456 consensus core genes in this strain and four closely related strains of complex, which were mainly involved in human diseases, metabolism, organismal systems, etc. Among the three aligned strains, the number of unique genes of this bacterium was the highest with a number of 171, and these genes were mainly associated with carbohydrate metabolism and cell growth and death. Resistance gene prediction demonstrated that the A5653 gene of this bacterium had double point mutations on the gene, but no tandem repeat mutations in the promoter region were detected. Furthermore, 12 genes belonging to the fungal multidrug resistance ATP-binding cassette (ABC) transporters were identified based on the complete genome sequence and phylogenetic analysis of A. lentulus, which belonged to the ALDp subfamily, the PDR subfamily (, , and ), and the MDR subfamily (), respectively, and there were four genes that are annotated to the major facilitator superfamily multidrug transporter. Further phylogenetic tree classification of the ABC transporter subfamilies predicted in the nine selected complex strains showed that these putative ABC proteins were divided into two main clusters, which belonged to the PDR (, , , and ) and MDR subfamilies (, , and ). The distribution of these ABC proteins varies among different species of the complex. The main result obtained from this study for the whole genome of provide new insights into better understanding the biological characteristics, pathogenicity, and resistance mechanisms of this bacterium. In this study, two resistance mechanisms, which include gene mutation and multidrug-resistant ABC transporter, were predicted in a single isolate. Based on the predicted site mutation combination, we speculate that the gene of may be partially responsible for azole resistance. Based on the predicted ABC transporter family genes, we hypothesize that resistance to multiple azoles in is mediated, at least in part, by these ABC transporters with resistance.