title: The chitin synthase genes chsA and chsC are not required for cell wall stress responses in the human pathogen Aspergillus fumigatus.
abstract: Invasive aspergillosis is a leading cause of mortality in immunocompromised patients. The fungal cell wall is an attractive antifungal target, but it is dynamic and responsive to external stressors. The existence of multiple chitin synthases within Aspergilli is thought to reflect specialized functions in cell wall damage responses that facilitate continued growth and viability. We previously reported increased transcription of Aspergillus fumigatus chitin synthases chsA and chsC following echinocandin treatment, suggesting important roles for these chitin synthases in cell wall compensation. As only partial disruptions have been made of these genes, we generated deletion mutants of chsA and chsC singly (ΔchsA and ΔchsC) and doubly (ΔchsA ΔchsC). The ΔchsA ΔchsC strain displayed reduced total chitin synthase activity. Interestingly, deletion of these chitin synthase genes did not affect levels of chitin or β-1,3-glucan.The ΔchsA, ΔchsC and ΔchsA ΔchsC strains produced wild-type echinocandin-mediated chitin increases, consistent with unaltered cell wall compensation. Furthermore, transcript levels of the remaining chitin synthase genes were unchanged in the mutant strains. Taken together, these results indicate that chsA and chsC do not play a direct role in the cell wall stress response. Our findings support the existence of complex post-transcriptional regulatory mechanisms controlling chitin biosynthetic machinery in response to cell wall damage.
authors.affiliation: Department of Pediatrics, Division of Pediatric Infectious Diseases, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Luise E
authors.initials: LE
authors.lastname: Rogg
authors.forename: Jarrod R
authors.initials: JR
authors.lastname: Fortwendel
authors.forename: Praveen Rao
authors.initials: PR
authors.lastname: Juvvadi
authors.forename: Amanda
authors.initials: A
authors.lastname: Lilley
authors.forename: William J
authors.initials: WJ
authors.lastname: Steinbach
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology; D001228:Aspergillosis / Q000382:microbiology*; D001232:Aspergillus fumigatus / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D002473:Cell Wall / Q000201:enzymology / Q000502:physiology* / Q000648:ultrastructure; D002687:Chitin Synthase / Q000235:genetics*; D054714:Echinocandins / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D013312:Stress, Physiological / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D002687:Chitin Synthase