title: A fungus-specific ras homolog contributes to the hyphal growth and virulence of Aspergillus fumigatus.
abstract: The Ras family of GTPase proteins has been shown to control morphogenesis in many organisms, including several species of pathogenic fungi. In a previous study, we identified a gene encoding a fungus-specific Ras subfamily homolog, rasB, in Aspergillus fumigatus. Here we report that deletion of A. fumigatus rasB caused decreased germination and growth rates on solid media but had no effect on total biomass accumulation after 24 h of growth in liquid culture. The DeltarasB mutant had an irregular hyphal morphology characterized by increased branching. Expression of rasBDelta113-135, a mutant transgene lacking the conserved rasB internal amino acid insertion, did not complement the deletion phenotype of delayed growth and germination rates and abnormal hyphal morphology. Virulence of the rasB deletion strain was diminished; mice infected with this strain exhibited approximately 65% survival compared to approximately 10% with wild-type and reconstituted strains. These data support the hypothesis that rasB homologs, which are highly conserved among fungi that undergo hyphal growth, control signaling modules important to the directional growth of fungal hyphae.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati, College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0529, USA.
authors.forename: Jarrod R
authors.initials: JR
authors.lastname: Fortwendel
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Ruchi
authors.initials: R
authors.lastname: Bhabhra
authors.forename: Steven
authors.initials: S
authors.lastname: Park
authors.forename: David S
authors.initials: DS
authors.lastname: Perlin
authors.forename: David S
authors.initials: DS
authors.lastname: Askew
authors.forename: Judith C
authors.initials: JC
authors.lastname: Rhodes
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001228:Aspergillosis / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D001232:Aspergillus fumigatus / Q000166:cytology / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity*; D018533:Biomass; D018929:Cell Culture Techniques; D002874:Chromosome Mapping; D015825:Chromosomes, Fungal; D004195:Disease Models, Animal; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005799:Genes, Dominant; D005800:Genes, Fungal; D011905:Genes, ras; D016681:Genome, Fungal; D025301:Hyphae / Q000166:cytology / Q000254:growth & development*; D007091:Image Processing, Computer-Assisted; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D016019:Survival Analysis; D013997:Time Factors; D019076:Transgenes; D014774:Virulence; D018631:ras Proteins / Q000737:chemistry
chemical_list: D018631:ras Proteins