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

Abstract

The opportunistic fungal pathogen Candida albicans has evolved a variety of mechanisms for surviving inside and escaping macrophages, including the initiation of filamentous growth. Although several distinct models have been proposed to explain this process at the molecular level, the signals driving hyphal morphogenesis in this context have yet to be clarified. Here, we evaluate the following three molecular signals as potential hyphal inducers within macrophage phagosomes: CO2, intracellular pH, and extracellular pH. Additionally, we revisit previous work suggesting that the intracellular pH of C. albicans fluctuates in tandem with morphological changes in vitro. Using time-lapse microscopy, we observed that C. albicans mutants lacking components of the CO2-sensing pathway were able to undergo hyphal morphogenesis within macrophages. Similarly, a rim101Δ strain was competent in hyphal induction, suggesting that neutral/alkaline pH sensing is not necessary for the initiation of morphogenesis within phagosomes either. Contrary to previous findings, single-cell pH-tracking experiments revealed that the cytosolic pH of C. albicans remains tightly regulated both within macrophage phagosomes and under a variety of in vitro conditions throughout the process of morphogenesis. This finding suggests that intracellular pH is not a signal contributing to morphological changes.