The Thm1 Zn(II)2 Cys6 transcription factor contributes to heat, membrane integrity and virulence in the insect pathogenic fungus Beauveria bassiana.

The ability to withstand heat and cell wall stress is critical for successful infection of target hosts by many pathogenic fungi. We report on the characterization of BbThm1 (transcription factor for heat and membrane integrity), a Zn(II)2 Cys6 (Gal4-like) family member, which regulates resistance to heat (32°C) and specific detergents in the insect pathogenic fungus, Beauveria bassiana. BbThm1 gene knock-out mutants showed severely impaired growth/resistance at 32°C and to SDS, but mild to moderate phenotypic responses to other stresses including oxidative, osmotic and cell-wall targeting compounds, or to various fungicides. Shifts in cell wall properties, adhesion and decreased viability were noted for the ΔBbThm1 mutant. Susceptibility to SDS but not heat could be rescued by exogenous ergosterol. Insect bioassays revealed decreased virulence of the ΔBbThm1 mutant against Galleria mellonella both topically and via intrahemocoel injection assays that correlated with impaired in insecta hyphal body formation and altered host immune prophenol oxidase (PO) activation. Transcriptomic analyses of the wild-type and ΔBbThm1 mutants revealed up-regulation of hydrolases but down-regulation of a wide range of basic metabolic processes. These data reveal fine tune aspects of the transcription factor network that regulates specific stress responses to contribute to the overall pathogenic process.