Conserved and Divergent Features of pH Sensing in Major Fungal Pathogens

PURPOSE OF REVIEW: For human fungal pathogens, sensory perception of extracellular pH is essential for colonisation of mammalian tissues and immune evasion. The molecular complexes that perceive and transmit the fungal pH signal are membrane-proximal and essential for virulence and are therefore of interest as novel antifungal drug targets. Intriguingly, the sensory machinery has evolved divergently in different fungal pathogens, yet spatial co-ordination of cellular components is conserved. RECENT FINDINGS: The recent discovery of a novel pH sensor in the basidiomycete pathogen Cryptococcus neformans highlights that, although the molecular conservation of fungal pH sensors is evolutionarily restricted, their subcellular localisation and coupling to essential components of the cellular ESCRT machinery are consistent features of the cellular pH sensing and adaptation mechanism. In both basidiomycetes and ascomycetes, the lipid composition of the plasma membrane to which pH sensing complexes are localised appears to have pivotal functional importance. Endocytosis of pH-sensing complexes occurs in multiple fungal species, but its relevance for signal transduction appears not to be universal. SUMMARY: Our overview of current understanding highlights conserved and divergent mechanisms of the pH sensing machinery in model and pathogenic fungal species, as well as important unanswered questions that must be addressed to inform the future study of such sensing mechanisms and to devise therapeutic strategies for manipulating them.