B bmsn2 acts as a pH ‐dependent negative regulator of secondary metabolite production in the entomopathogenic fungus B eauveria bassiana

Summary Fungal secondary metabolites are chemical compounds important for development, environmental adaptation and for potential biotechnological and pharmaceutical applications. Oosporein, a red‐pigmented benzoquinone, produced by many fungal insect pathogenic B eauveria spp., shows remarkable functional diversity, displaying antimicrobial, antiviral and even anti‐proliferative activities. A homologue of the msn2 / seb1 transcription factor was identified in a B eauveria bassiana random T‐DNA insertion library. Targeted gene‐knockout of B bmsn2 resulted in reduced growth and increased sensitivity to C alcofluor W hite, H 2 O 2 and C ongo R ed. However, when normalized to growth at 26° C , the Δ B bmsn2 mutant was more tolerant to high temperature (32° C ) than the wild type parent. The Δ B bmsn2 mutant also displayed a pH ‐dependent growth phenotype, with little growth seen at pH  < 5.0 but, better growth at alkaline conditions ( pH  > 8.0). Unexpectedly, a pH ‐dependent deregulation of a red pigment, identified as oosporein, was seen in the Δ B bmsn2 mutant. The Δ B bmsn2 strain was impaired in virulence in both topical and intrahaemocoel injection bioassays against G alleria mellonella . Δ B bmsn2 proliferation in the host haemolymph and conidiation on the host cadaver was reduced. These data indicate that B bmsn2 acts as a negative regulator of oosporein production and contributes to virulence and growth in response to external pH in B . bassiana .