Dysregulation of Key Proteinases in Aspergillus fumigatus Induced by Blood Platelets

Background: Aspergillus fumigatus is the most common species causing invasive aspergillosis (IA), a life-threatening infection with more than ۸۰% mortality. Interactions between A. fumigatus and human blood platelets lead to intravascular thrombosis and localized infarcts. To better understand A. fumigatus pathogenesis, we aimed to analyze the genetic basis of interactions between the pathogen and blood platelets. Methods: A bioinformatic pipeline on microarray gene expression dataset, including analysis of differentially expressed genes (DEGs) using Limma R package and their molecular function, as well as biological pathways identification, was conducted to find the effective genes involved in IA. In the wet phase, the gene expression patterns following fungal exposure to blood platelets at ۱۵, ۳۰, ۶۰, and ۱۸۰ min were evaluated by quantitative reverse transcriptase-PCR analysis. Results: Three genes encoding aspartic endopeptidases including (Pep۱), (Asp f ۱۳), and (β-glucanase) were the standing candidates. The invasion-promoting fungal proteinase-encoding genes were down-regulated after ۳۰ min of hyphal incubation with blood platelets, and then up-regulated at ۶۰ and ۱۸۰ min, although only Pep۱ was greater than the control at the ۶۰and ۱۸۰ min time points. Also, the same genes were downregulated in more the clinical isolates relative to the standard strain CBS ۱۴۴.۸۹. Conclusions: Our findings delineate the possible induction of fungal-encoded proteinases by blood platelets. This provides a new research line into A. fumigatus’ molecular pathogenesis. Such insight into IA pathogenesis might also guide researchers toward novel platelet-based therapies that involve molecular interventions, especially in IA patients.

Keywords:

Aspergillus fumigatus , Blood Platelets , Gene Expression , Microarray Analysis , Proteinases.