title: The Aspergillus fumigatus septins play pleiotropic roles in septation, conidiation, and cell wall stress, but are dispensable for virulence.
abstract: Septins are a conserved family of GTPases that regulate important cellular processes such as cell wall integrity, and septation in fungi. The requirement of septins for virulence has been demonstrated in the human pathogenic yeasts Candida albicans and Cryptococcus neoformans, as well as the plant pathogen Magnaporthe oryzae. Aspergillus spp. contains five genes encoding for septins (aspA-E). While the importance of septins AspA, AspB, AspC, and AspE for growth and conidiation has been elucidated in the filamentous fungal model Aspergillus nidulans, nothing is known on the role of septins in growth and virulence in the human pathogen Aspergillus fumigatus. Here we deleted all five A. fumigatus septins, and generated certain double and triple septin deletion strains. Phenotypic analyses revealed that while all the septins are dispensable in normal growth conditions, AspA, AspB, AspC and AspE are required for regular septation. Furthermore, deletion of only the core septin genes significantly reduced conidiation. Concomitant with the absence of an electron-dense outer conidial wall, the ΔaspB strain was also sensitive to anti-cell wall agents. Infection with the ΔaspB strain in a Galleria mellonella model of invasive aspergillosis showed hypervirulence, but no virulence difference was noted when compared to the wild-type strain in a murine model of invasive aspergillosis. Although the deletion of aspB resulted in increased release of TNF-α from the macrophages, no significant inflammation differences in lung histology was noted between the ΔaspB strain and the wild-type strain. Taken together, these results point to the importance of septins in A. fumigatus growth, but not virulence in a murine model.
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, United States.
authors.forename: José M
authors.initials: JM
authors.lastname: Vargas-Muñiz
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, United States.
authors.forename: Hilary
authors.initials: H
authors.lastname: Renshaw
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, NC, United States.
authors.forename: Amber D
authors.initials: AD
authors.lastname: Richards
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, NC, United States; Service of Infectious Diseases, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland; Institute of Microbiology, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lamoth
authors.affiliation: Duke Proteomics and Metabolomics Core Facility, Center for Genomic and Computational Biology, Duke University, Durham, NC, United States.
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Soderblom
authors.affiliation: Duke Proteomics and Metabolomics Core Facility, Center for Genomic and Computational Biology, Duke University, Durham, NC, United States.
authors.forename: M Arthur
authors.initials: MA
authors.lastname: Moseley
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, NC, United States.
authors.forename: Praveen R
authors.initials: PR
authors.lastname: Juvvadi
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, United States; Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, NC, United States. Electronic address: bill.steinbach@duke.edu.
authors.forename: William J
authors.initials: WJ
authors.lastname: Steinbach
mesh_terms: D000818:Animals; D001228:Aspergillosis / Q000382:microbiology / Q000473:pathology; D001232:Aspergillus fumigatus / Q000235:genetics / Q000502:physiology*; D002455:Cell Division; D002473:Cell Wall / Q000378:metabolism*; D004195:Disease Models, Animal; D017353:Gene Deletion; D007915:Lepidoptera / Q000382:microbiology / Q000502:physiology; D051379:Mice; D058112:Septins / Q000235:genetics / Q000378:metabolism*; D013172:Spores, Fungal / Q000254:growth & development*; D014774:Virulence
chemical_list: D058112:Septins
keywords: Aspergillus fumigatus; Cell wall; Conidiation; Septation; Septins; Virulence