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Updated: Jul 19, 2025

Measurement of Vacuolar and Cytosolic pH In Vivo in Yeast Cell Suspensions
Published on: April 19, 2013
Conserved and Divergent Features of pH Sensing in Major Fungal Pathogens
Shadab Farhadi Cheshmeh Morvari1, Bethany L McCann2, Elaine M Bignell2
1Manchester Fungal Infection Group, University of Manchester, Grafton Street, Manchester, M13 9NT UK.
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.
Insights
Fungal pathogens sense external pH using conserved cellular machinery, crucial for infection and immune evasion. Understanding these pH sensors offers new antifungal drug targets.
Area of Science:
- Microbiology
- Molecular Biology
- Pathogenesis
Background:
- Extracellular pH sensing is vital for fungal pathogens to colonize hosts and evade immune responses.
- The molecular complexes involved are membrane-proximal, essential for virulence, and represent potential antifungal drug targets.
- Fungal pH sensing machinery shows divergent evolution across species, yet spatial coordination of cellular components is conserved.
Purpose of the Study:
- To review conserved and divergent mechanisms of pH sensing in fungal pathogens.
- To highlight the importance of pH sensing for fungal virulence and host interaction.
- To identify unanswered questions for future research and therapeutic strategy development.
Main Methods:
- Comparative analysis of pH sensing mechanisms across diverse fungal species.
- Review of recent discoveries, including novel pH sensors in *Cryptococcus neoformans*.
- Examination of the role of cellular ESCRT machinery and plasma membrane lipid composition.
Main Results:
- A novel pH sensor in *Cryptococcus neoformans* exemplifies restricted molecular conservation but conserved subcellular localization and coupling to the ESCRT machinery.
- Plasma membrane lipid composition plays a critical role in the function of pH sensing complexes.
- Endocytosis of pH-sensing complexes is observed in multiple species, but its role in signal transduction is not universal.
Conclusions:
- Fungal pH sensing involves both conserved and divergent molecular mechanisms.
- Understanding these mechanisms is key to developing novel antifungal therapies targeting virulence factors.
- Further research is needed to fully elucidate these pathways and their therapeutic potential.
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