The two-component histidine kinases DrkA and SlnA are required for in vivo growth in the human pathogen Penicillium marneffei.

In order to cause disease fungal pathogens must be capable of evading or tolerating the host immune defence system. One commonly utilized evasion mechanism is the ability to continually reside within macrophages of the innate immune system and survive subsequent phagocytic destruction. For intracellular growth to occur, fungal pathogens which typically grow in a filamentous hyphal form in the environment must be able to switch growth to a unicellular yeast growth form in a process known as dimorphic switching. The cue to undergo dimorphic switching relies on the recognition of, and response to, the intracellular host environment. Two-component signalling systems are utilized by eukaryotes to sense and respond to changes in the external environment. This study has investigated the role of the hybrid histidine kinase components encoded by drkA and slnA, in the dimorphic pathogen Penicillium marneffei. Both SlnA and DrkA are required for stress adaptation but are uniquely required for different aspects of asexual development, hyphal morphogenesis and cell wall integrity. Importantly, slnA and drkA are both essential for the generation of yeast cells in vivo, with slnA required for the germination of conidia and drkA required for dimorphic switching during macrophage infection.