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Fungal adenylyl cyclase integrates CO2 sensing with cAMP signaling and virulence

Torsten Klengel1, Wei-Jun Liang, James Chaloupka

  • 1Department of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, United Kingdom.

Current Biology : CB
|November 24, 2005
PubMed

Insights

Carbon dioxide (CO2) and bicarbonate (HCO3-) directly stimulate fungal virulence pathways by activating adenylyl cyclase. This CO2 sensing mechanism is conserved in pathogenic fungi like Candida albicans and Cryptococcus neoformans, offering new therapeutic targets.

Area of Science:

  • Mycology
  • Molecular Biology
  • Pathogenesis

Background:

  • Candida albicans and Cryptococcus neoformans are significant fungal pathogens in immunocompromised individuals.
  • Morphological changes, such as filamentation in C. albicans and capsule formation in C. neoformans, are critical virulence factors.
  • These processes are regulated by cyclic adenosine 3',5'-monophosphate (cAMP) signaling, mediated by adenylyl cyclase.

Purpose of the Study:

  • To investigate the role of carbon dioxide (CO2) and bicarbonate (HCO3-) in fungal morphology and pathogenesis.
  • To determine if CO2/HCO3- sensing is linked to cAMP signaling and adenylyl cyclase activity in pathogenic fungi.
  • To explore the potential of targeting this pathway for novel antifungal therapies.

Main Methods:

  • Assessed the effect of physiological CO2/HCO3- concentrations on C. albicans filamentation.
  • Investigated the role of carbonic anhydrase in C. albicans pathogenesis using in vivo models.
  • Examined the sensitivity of C. neoformans adenylyl cyclase to CO2/HCO3-.

Main Results:

  • Physiological concentrations of CO2/HCO3- directly stimulate adenylyl cyclase activity, inducing filamentation in C. albicans.
  • Carbonic anhydrase activity is essential for C. albicans virulence in CO2-limited environments.
  • Adenylyl cyclase from C. neoformans is also sensitive to CO2/HCO3-, indicating conserved signaling.

Conclusions:

  • A conserved link exists between cAMP signaling and CO2/HCO3- sensing in pathogenic fungi.
  • CO2 sensing is a critical mediator of fungal pathogenesis, influencing key virulence attributes.
  • The identified CO2-sensing pathway represents a promising target for developing new antifungal treatments.

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