ABSTRACT
Aspergillus fumigatus is one of the most common pathogenic fungi, which results in high morbidity and mortality in immunocompromised patients. Amphotericin B (AMB) is used as the core drug for the treatment of triazole-resistant A. fumigatus. Following the usage of amphotericin B drugs, the number of amphotericin B-resistant A. fumigatus isolates showed an increasing trend over the years, but the mechanism and mutations associated with amphotericin B sensitivity are not fully understood. In this study, we performed a k-mer-based genome-wide association study (GWAS) in 98 A. fumigatus isolates from public databases. Associations identified with k-mers not only recapitulate those with SNPs but also discover new associations with insertion/deletion (indel). Compared to SNP sites, the indel showed a stronger association with amphotericin B resistance, and a significant correlated indel is present in the exon region of AFUA_7G05160, encoding a fumarylacetoacetate hydrolase (FAH) family protein. Enrichment analysis revealed sphingolipid synthesis and transmembrane transport may be related to the resistance of A. fumigatus to amphotericin B. The expansion of variant types detected by the k-mer method increases opportunities to identify and exploit complex genetic variants that drive amphotericin B resistance, and these candidate variants help accelerate the selection of prospective gene markers for amphotericin B resistance screening in A. fumigatus.
ABSTRACT
Two new isoaurones derivatives were obtained from Callistephus chinensis flower. Their structures were elucidated on the basis of extensive spectroscopic analyses. Both of the new compounds were evaluated cytotoxic activity. Phytochemical investigation of Callistephus chinensis flower led to the isolation of two new isoaurones derivatives (Z)-4',4,10-trihydroxy-siamaurone (1) and (E)-4',4,10-trihydroxy-siamaurone (2). The structures of these new compounds were identified by the interpretation of spectroscopic data (mainly 1D and 2D NMR) and by comparison with data reported in the literature. Both of the new compounds were evaluated for their cytotoxicity.
