TCA cycle-related lactate and malate dehydrogenases differentially modulate fungal development, immune evasion and pathogenicity in the entomopathogen Beauveria bassiana

The tricarboxylic acid (TCA) cycle plays a pivotal role in fungal physiological processes. In this study, two TCA-cycle related enzyme were functionally analyzed in a model entomopathogenic fungus Beauveria bassiana, including NAD-dependent lactate dehydrogenase (BbLdh) and malate dehydrogenase (BbMdh1 and 2). Domain annotation indicated all these enzymes contained an Ldh_1 domain. Functional analyses indicated that BbLdh and BbMdh2 had differential contributions to fungal growth, development, stress tolerance, virulence, and mycosis. Notably, BbLdh played a more important role in fungal interaction with the host than BbMdh2, which was attributed to its additional functions in stress tolerance, extracellular acidification, in vivo development, and immune evasion. In contrast, BbMdh2 primarily was involved in cuticle penetration due to its roles in utilization of host nutrients (e.g., lipids and proteins). Comparative transcriptomic analysis revealed that BbLdh mediated numerous metabolic pathways and physiological responses to oxidative stress. Collectively, this study reveals the metabolic mechanisms involved in the B. bassiana adaptation to the host niches, deepening our understanding of metabolic pathways during fungal interaction with the hosts.