Candida albicans Hyphal Morphogenesis within Macrophages Does Not Require Carbon Dioxide or pH-Sensing Pathways

Area of Science:

• Medical Mycology
• Cellular Microbiology
• Infectious Diseases

Background:

• Candida albicans, an opportunistic fungal pathogen, employs filamentous growth (hyphal morphogenesis) to survive and escape host macrophages.
• Understanding the signals that induce hyphal growth within macrophages is crucial for developing targeted antifungal therapies.

Purpose of the Study:

• To investigate the roles of carbon dioxide (CO2), intracellular pH, and extracellular pH as potential inducers of Candida albicans hyphal morphogenesis within macrophage phagosomes.
• To re-evaluate the relationship between intracellular pH fluctuations and morphological changes in C. albicans.

Main Methods:

• Utilized time-lapse microscopy to observe hyphal morphogenesis in C. albicans within macrophages.
• Assessed hyphal induction in C. albicans mutants deficient in CO2-sensing pathways.
• Examined the hyphal induction capacity of a rim101Δ strain, which is involved in pH sensing.
• Performed single-cell pH-tracking experiments to monitor cytosolic pH dynamics during morphogenesis both in vitro and within macrophages.

Main Results:

• C. albicans mutants lacking CO2-sensing pathway components successfully underwent hyphal morphogenesis within macrophages.
• A rim101Δ mutant strain was also competent for hyphal induction, indicating neutral/alkaline pH sensing is not essential.
• Cytosolic pH of C. albicans remained tightly regulated under various conditions, including within macrophage phagosomes, contradicting previous findings.

Conclusions:

• CO2 sensing and intracellular pH regulation are not the primary signals initiating Candida albicans hyphal morphogenesis within macrophages.
• Intracellular pH does not appear to be a direct signal contributing to morphological changes during fungal-host interactions.