RRC ID 52793
Author Pereira Silva L, Alves de Castro P, Dos Reis TF, Paziani MH, Von Zeska Kress MR, Riaño-Pachón DM, Hagiwara D, Ries LN, Brown NA, Goldman GH.
Title Genome-wide transcriptome analysis of Aspergillus fumigatus exposed to osmotic stress reveals regulators of osmotic and cell wall stresses that are SakAHOG1 and MpkC dependent.
Journal Cell Microbiol
Abstract Invasive aspergillosis is predominantly caused by Aspergillus fumigatus, and adaptations to stresses experienced within the human host are a prerequisite for the survival and virulence strategies of the pathogen. The central signal transduction pathway operating during hyperosmotic stress is the high osmolarity glycerol mitogen-activated protein kinase cascade. A. fumigatus MpkC and SakA, orthologues of the Saccharomyces cerevisiae Hog1p, constitute the primary regulator of the hyperosmotic stress response. We compared A. fumigatus wild-type transcriptional response to osmotic stress with the ΔmpkC, ΔsakA, and ΔmpkC ΔsakA strains. Our results strongly indicate that MpkC and SakA have independent and collaborative functions during the transcriptional response to transient osmotic stress. We have identified and characterized null mutants for four A. fumigatus basic leucine zipper proteins transcription factors. The atfA and atfB have comparable expression levels with the wild-type in ΔmpkC but are repressed in ΔsakA and ΔmpkC ΔsakA post-osmotic stress. The atfC and atfD have reduced expression levels in all mutants post-osmotic stress. The atfA-D null mutants displayed several phenotypes related to osmotic, oxidative, and cell wall stresses. The ΔatfA and ΔatfB were shown to be avirulent and to have attenuated virulence, respectively, in both Galleria mellonella and a neutropenic murine model of invasive pulmonary aspergillosis.
Volume 19(4)
Published 2016-10-30
DOI 10.1111/cmi.12681
PMID 27706915
MeSH Animals Aspergillosis / microbiology* Aspergillus fumigatus / enzymology* Aspergillus fumigatus / genetics Cell Wall Female Fungal Proteins / genetics* Fungal Proteins / metabolism Gene Expression Profiling Gene Expression Regulation, Fungal Gene Ontology Genome, Fungal Mice, Inbred BALB C Mitogen-Activated Protein Kinases / genetics* Mitogen-Activated Protein Kinases / metabolism Osmotic Pressure Signal Transduction Stress, Physiological Transcription Factors / physiology Transcriptome*
IF 3.43
Times Cited 19
Pathogenic microorganisms