Regulatory pathway and function of pathogenic factors in human fungus: genomic or transcriptomic strategy?
Scientists have been devoted to the study on microbial pathogenity through the regulatory mechanism and function of important genes. The next generation sequencing technology has provided us various strategies with genomic and transcriptomic analyses as dominant. However, which strategy to use has arise to a debate. In this study, the investigation on the regulatory pathway and function of two pathogenic factors in human fungus Candida albicans gives us some clues. Firstly, we confirmed the characteristics of BLP1 in vitro and in vivo by determination the repression of BLP1 gene expression in C. albicans by glucose phenotypically and genetically. Evidence on the important role of BLP1 for vaginal immunopathogenesis had also been presented. Secondly, using whole genome and targeted sequencing approaches, we determined that a number of clinical is olates, including strain 529L, harbor a similarly expressed, yet distinct Ece1p isoform variant that encodes for a predicted functional candidalysin. Creation of an isogenic panel of chimeric strains harboring swapped Ece1p peptides or HiBiT tags revealed a secretion defect encoded by the 529L ORF that was associated with reduced virulence. A genetic survey of over 100 clinical isolates showed a conserved linkage between Ece1p P2 and P3 sequences, suggesting that substrate specificity around Kex2p-mediated KR cleavage sites involved in protein secretion may contribute to differential pathogenicity amongst clinical isolates.