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.

Abstract

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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