Modulation of Phagosomal pH by Promotes Hyphal Morphogenesis and Requires Stp2p, a Regulator of Amino Acid Transport

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The innate immune system represents a key barrier that fungal pathogens such as Candida albicans must overcome in order to disseminate through the host. C. albicans cells phagocytosed by macrophages initiate a complex program that involves a large-scale reprogramming of metabolism and transcription and results in the switch to a hyphal form that can penetrate and kill the macrophage. Though a number of signals are known to induce this morphological transition in vitro, what does so following phagocytosis has been unclear. We previously showed that C. albicans rapidly neutralizes acidic, nutrient-poor media that resembles the phagolysosome and that this is deficient in mutants impaired in amino acid import due to a mutation in STP2. In this paper, we investigate whether this happens within the macrophage as well. We show here that, in contrast to wild-type cells, stp2Δ mutants occupy an acidic phagosome and are unable to initiate hyphal differentiation. Because of this, they are more sensitive to killing and do less damage to the macrophages than cells that can neutralize the phagolysosome. We conclude that alteration of phagosomal pH is an important virulence adaptation in this species.

Vyšlo v časopise: Modulation of Phagosomal pH by Promotes Hyphal Morphogenesis and Requires Stp2p, a Regulator of Amino Acid Transport. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1003995
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003995

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