Bahareh Arghavan1, Mohammad Shafiee2,3, Seyed Jamal Hashemi1, Sadegh Khodavaisy1, Nazanin Hosseinkhan4, Mojtaba Didehdar5, Muhammad Getso1,6, Aliasghar Ayatollahi7, Sassan Rezaie1. 1. Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. 2. Department of Medical Laboratory Sciences, Khomein University of Medical Sciences, Khomein, Iran. 3. Stem Cell Research Center, Golestan University of Medical Sciences, Gorgan, Iran. 4. Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran. 5. Department of Parasitology and Mycology, School of Medicine, Arak University of Medical Sciences, Arak, Iran. 6. Department of Medical Microbiology and Parasitology, College of Health Sciences, Bayero University, Kano, Nigeria. 7. Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
Abstract
BACKGROUND: Aspergillus fumigatus is the most common species causing invasive aspergillosis (IA), a life-threatening infection with more than 80% 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 15, 30, 60, and 180 min were evaluated by quantitative reverse transcriptase-PCR analysis. RESULTS: Three genes encoding aspartic endopeptidases including (Pep1), (Asp f 13), and (β-glucanase) were the standing candidates. The invasion-promoting fungal proteinase-encoding genes were down-regulated after 30 min of hyphal incubation with blood platelets, and then up-regulated at 60 and 180 min, although only Pep1 was greater than the control at the 60and 180 min time points. Also, the same genes were downregulated in more the clinical isolates relative to the standard strain CBS 144.89. CONCLUSION: 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.
BACKGROUND: Aspergillus fumigatus is the most common species causing invasive aspergillosis (IA), a life-threatening infection with more than 80% 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 15, 30, 60, and 180 min were evaluated by quantitative reverse transcriptase-PCR analysis. RESULTS: Three genes encoding aspartic endopeptidases including (Pep1), (Asp f 13), and (β-glucanase) were the standing candidates. The invasion-promoting fungal proteinase-encoding genes were down-regulated after 30 min of hyphal incubation with blood platelets, and then up-regulated at 60 and 180 min, although only Pep1 was greater than the control at the 60and 180 min time points. Also, the same genes were downregulated in more the clinical isolates relative to the standard strain CBS 144.89. CONCLUSION: 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.
Authors: Charles O Morton; John J Varga; Anke Hornbach; Markus Mezger; Helga Sennefelder; Susanne Kneitz; Oliver Kurzai; Sven Krappmann; Hermann Einsele; William C Nierman; Thomas R Rogers; Juergen Loeffler Journal: PLoS One Date: 2011-01-14 Impact factor: 3.240