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A ceramide synthase is important for filamentous fungal biofilm morphology and antifungal drug susceptibility

ABSTRACT: The complex structure of the biofilm generates microenvironments which impact the fitness of the biofilm community as a whole. Contributions to fitness include the development of emergent properties resulting in the recalcitrance to external stressors such as environmental stress or drug stress in the context of a pathogen. The biofilm developed by the filamentous fungal pathogen Aspergillus fumigatus develops zones of low oxygen which contribute to a reduction in antifungal drug susceptibility, however the mechanisms driving this have remained elusive. Here we have utilized a transcriptomic approach to probe the biofilm structure in comparison to a planktonic lifestyle to identify unique biofilm transcriptional patterns. Importantly we utilized two phenotypically diverse strains. From this analysis we have identified biofilm specific gene co-expression networks as well as a ceramide synthase, designated barA, with a striking increase in transcript abundance specifically in the biofilm. Null mutants for barA in two strain backgrounds display altered biofilm morphology with some strain specific differences but interestingly do not impact virulence. Importantly we find the BarA ceramide synthase has a role in regulating susceptibility to classes of ergosterol targeting antifungal drugs. In the absence of barA, treatment with voriconazole leads to significant cellular damage in the form of lysis. Through this we have identified a novel mechanism driving antifungal drug resistance in the biofilm of filamentous fungal pathogen.

ORGANISM(S): Aspergillus fumigatus

PROVIDER: GSE325906 | GEO | 2026/05/01

REPOSITORIES: GEO

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A ceramide synthase is important for filamentous fungal biofilm morphology and antifungal drug susceptibility

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