Pleiotropic Roles of LAMMER Kinase, Lkh1 in Stress Responses and Virulence of

Dual-specificity LAMMER kinases are highly evolutionarily conserved in eukaryotes and play pivotal roles in diverse physiological processes, such as growth, differentiation, and stress responses. Although the functions of LAMMER kinase in fungal pathogens in pathogenicity and stress responses have been characterized, its role in , a human fungal pathogen and a model yeast of basidiomycetes, remains elusive. In this study, we identified a homologous gene and constructed a strain with a deleted and a complemented strain. Similar to other fungi, the Δ mutant showed intrinsic growth defects. We observed that Lkh1 was involved in diverse stress responses, including oxidative stress and cell wall stress. Particularly, Lkh1 regulates DNA damage responses in Rad53-dependent and -independent manners. Furthermore, the absence of reduced basidiospore formation. Our observations indicate that Lkh1 becomes hyperphosphorylated upon treatment with rapamycin, a TOR protein inhibitor. Notably, deletion led to defects in melanin synthesis and capsule formation. Furthermore, we found that the deletion of led to the avirulence of in a systemic cryptococcosis murine model. Taken together, Lkh1 is required for the stress response, sexual differentiation, and virulence of .