Deletion of the sec4 Homolog srgA from Aspergillus fumigatus Is Associated with an Impaired Stress Response, Attenuated Virulence and Phenotypic Heterogeneity
Open Access
- 13 June 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (6), e66741
- https://doi.org/10.1371/journal.pone.0066741
Abstract
Small GTPases of the Rab family are master regulators of membrane trafficking, responsible for coordinating the sorting, packaging and delivery of membrane-bound vesicles to specific sites within eukaryotic cells. The contribution of these proteins to the biology of the human pathogenic fungus Aspergillus fumigatus has not been explored. In this study, we characterized the srgA gene, encoding a Rab GTPase closely related to Sec4. We found that a GFP-SrgA fusion protein accumulated preferentially at hyphal tips and mature condiophores. The radial growth of a ΔsrgA mutant was impaired on both rich and minimal medium, consistent with a role for SrgA in filamentous growth. In addition, the ΔsrgA mutant revealed dysmorphic conidiophores that produced conidia with heterogeneous morphology. The ΔsrgA mutant was hypersensitive to brefeldin A-mediated inhibition of vesicular trafficking and showed increased temperature sensitivity relative to wild type A. fumigatus. However, the most striking phenotype of this mutant was its phenotypic heterogeneity. Individual colonies isolated from the original ΔsrgA mutant showed variable morphology with colony sectoring. In addition, each isolate of the ΔsrgA mutant displayed divergent phenotypes with respect to thermotolerance, in vitro stress response and virulence in a Galleria mellonella infection model. Taken together, these results indicate that SrgA contributes to the asexual development and filamentous growth of A. fumigatus. However, the discordant phenotypes observed among individual isolates of the ΔsrgA mutant suggest that the absence of srgA exerts selective pressure for the acquisition of compensatory changes, such as second-site suppressor mutations.Keywords
This publication has 38 references indexed in Scilit:
- Effects of a Defective Endoplasmic Reticulum-Associated Degradation Pathway on the Stress Response, Virulence, and Antifungal Drug Susceptibility of the Mold Pathogen Aspergillus fumigatusEukaryotic Cell, 2013
- HacA-Independent Functions of the ER Stress Sensor IreA Synergize with the Canonical UPR to Influence Virulence Traits in Aspergillus fumigatusPLoS Pathogens, 2011
- Polarized growth in fungi: Symmetry breaking and hyphal formationSeminars in Cell & Developmental Biology, 2011
- Spitzenkörper, Exocyst, and Polarisome Components in Candida albicans Hyphae Show Different Patterns of Localization and Have Distinct Dynamic PropertiesEukaryotic Cell, 2010
- Hyphal growth in Candida albicans requires the phosphorylation of Sec2 by the Cdc28-Ccn1/Hgc1 kinaseThe EMBO Journal, 2010
- A Role for the Unfolded Protein Response (UPR) in Virulence and Antifungal Susceptibility in Aspergillus fumigatusPLoS Pathogens, 2009
- Synthetic lethality between eIF5A and Ypt1 reveals a connection between translation and the secretory pathway in yeastMolecular Genetics and Genomics, 2008
- Hyphal Growth: a Tale of Motors, Lipids, and the SpitzenkörperEukaryotic Cell, 2007
- A Eukaryotic Capsular Polysaccharide Is Synthesized Intracellularly and Secreted via ExocytosisMolecular Biology of the Cell, 2006
- Brefeldin A: Deciphering an Enigmatic Inhibitor of SecretionPlant Physiology, 2002