rtfA controls development, secondary metabolism, and virulence in Aspergillus fumigatus

• Published in: PloS one 2017-04, Vol.12 (4), p.e0176702
• Main Authors: Myers, Ryan R, Smith, Timothy D, Elsawa, Sherine F, Puel, Olivier, Tadrist, Souraia, Calvo, Ana M
• Format: Article
• Language: English
• Subjects: Aflatoxin B1; Airborne microorganisms; Alkaloids; Allergic bronchopulmonary aspergillosis; Animal models; Animals; Apoptosis; Aspergillosis; Aspergillus; Aspergillus fumigatus; Aspergillus fumigatus - pathogenicity; Aspergillus fumigatus - physiology; Asthma; Biodegradation; Biofilms; Biology and Life Sciences; Breast cancer; Cell Adhesion - physiology; Cell Wall - metabolism; Chemotherapy; Cloning; Complications; Composting; Defensive behavior; Degradation; Deoxyribonucleic acid; Disease Models, Animal; DNA; DNA methylation; DNA-directed RNA polymerase; Drugs; Enzymes; Female; Fungal Proteins - genetics; Fungal Proteins - metabolism; Fungi; Galleria mellonella; Genes; Genetic aspects; Genetic Engineering; Glucose; Hematology; Infections; Insects; Life Sciences; Localization; Lung diseases; Medicine and Health Sciences; Metabolism; Metabolites; Mice; Mice, Inbred ICR; Morphogenesis; Moths; Municipalities; Mycology; Opportunist infection; Oxidative stress; Oxidative Stress - physiology; Pathogenicity; Pathogens; Peptide Hydrolases - metabolism; Physiological aspects; Protein turnover; Proteins; Research and Analysis Methods; RNA polymerase; RNA polymerase II; Saccharides; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Secondary Metabolism; Secondary metabolites; Stem cells; TATA-Box Binding Protein - genetics; TATA-Box Binding Protein - metabolism; Toxicology; Transcription Factors - genetics; Transcription Factors - metabolism; Virulence; Virulence (Microbiology); Virulence - physiology; Yard waste; Yeast
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0176702

Invasive aspergillosis by Aspergillus fumigatus is a leading cause of infection-related mortality in immune-compromised patients. In order to discover potential genetic targets to control A. fumigatus infections we characterized rtfA, a gene encoding a putative RNA polymerase II transcription elongation factor-like protein. Our recent work has shown that the rtfA ortholog in the model fungus Aspergillus nidulans regulates morphogenesis and secondary metabolism. The present study on the opportunistic pathogen A. fumigatus rtfA gene revealed that this gene influences fungal growth and conidiation, as well as production of the secondary metabolites tryptoquivaline F, pseurotin A, fumiquinazoline C, festuclavine, and fumigaclavines A, B and C. Additionally, rtfA influences protease activity levels, the sensitivity to oxidative stress and adhesion capacity, all factors important in pathogenicity. Furthermore, rtfA was shown to be indispensable for normal virulence using Galleria mellonella as well as murine infection model systems.