Environmental pH modulation by pathogenic fungi as a strategy to conquer the host
Fig 2
Neutralization of the macrophage phagosome by the fungal pathogen C. albicans is essential for host damage.
Upon phagocytosis by the macrophages, C. albicans responds to the presence of amino acids and other alternative carbon sources abundant in the phagosomal milieu. Amino acids (AA) in particular are sensed via the SPS sensor system (orange), leading to activation of the transcription factor Stp2p, which induces the expression of genes encoding for amino acid permeases (green rectangles) and ammonium transporters (purple rectangles). This results in uptake of amino acids into and release of NH4+ from the fungal cell and increase of phagosomal pH. Hyphal growth causes physical damage to the macrophage membranes, leading to leakage of cellular content and death. C. albicans cells defective in utilization of amino acids and/or extrusion of NH4+, such as the stp2Δ mutant, fail to modulate the pH of the phagosome and are readily cleared by the immune cells.