Phosphate in Virulence of Candida albicans and Candida glabrata

Abstract

Candida species are the most commonly isolated invasive human fungal pathogens. A role for phosphate acquisition in their growth, resistance against host immune cells, and tolerance of important antifungal medications is becoming apparent. Phosphorus is an essential element in vital components of the cell, including chromosomes and ribosomes. Producing the energy currency of the cell, ATP, requires abundant inorganic phosphate. A comparison of the network of regulators and effectors that controls phosphate acquisition and intracellular distribution, the PHO regulon, between the model yeast Saccharomyces cerevisiae, a plant saprobe, its evolutionarily close relative C. glabrata, and the more distantly related C. albicans, highlights the need to coordinate phosphate homeostasis with adenylate biosynthesis for ATP production. It also suggests that fungi that cope with phosphate starvation as they invade host tissues, may link phosphate acquisition to stress responses as an efficient mechanism of anticipatory regulation. Recent work indicates that connections among the PHO regulon, Target of Rapamycin Complex 1 signaling, oxidative stress management, and cell wall construction are based both in direct signaling links, and in the provision of phosphate for sufficient metabolic intermediates that are substrates in these processes. Fundamental differences in fungal and human phosphate homeostasis may offer novel drug targets.

A Biodegradable Antifungal-Loaded Sol–Gel Coating for the Prevention and Local Treatment of Yeast Prosthetic-Joint Infections

“…This effect may be related to the hydrolytic degradation of the coatings. During sol–gel hydrolytic degradation, phosphate ions are released to media, which are virulence and morphogenesis modulating factors in some yeasts such as C. albicans and C. glabrata [ 40 , 41 ].…”

A dissemination-prone morphotype enhances extrapulmonary organ entry by the fungusCryptococcus neoformans

“…Also, suppressing phosphate acquisition by deleting the pho4 gene limited phenotypic heterogeneity in vivo: neither large nor small morphotypes appeared in mouse lungs. Phosphate is essential for cell homeostasis and growth, and its acquisition is tightly controlled in microbes that absorb fluctuating levels of phosphate from their surroundings (Köhler et al, 2020;Lev and Djordjevic, 2018). Phosphate is also critical for Candida albicans morphogenesis (hyphal formation), stress resistance, and tissue invasion (Ikeh et al, 2016;Liu et al, 2018).…”

Candida glabrata Antifungal Resistance and Virulence Factors, a Perfect Pathogenic Combination

“…The genus Candida species can induce their capture through phagocytes in endothelial and epithelial cells, using them as a “safe home”, preventing the maturation of the phagolysosome and its destruction [ 72 , 77 ]. It has been reported that C. glabrata can survive within the phagosome due to its ability to generate strong stress responses against ROS, neutralizing the phagocytic environment and thus escaping phagocytosis [ 72 , 77 , 78 , 79 , 80 ]. Such a phenomenon requires the activation of different genes in the pathogen ( Skn7p , Yap1p , Msn2p , and Msn4p ) [ 76 , 81 , 82 ] that encode proteins (Transcription factors Skn7, CgYap1, MSN2p, MSN4p) involved in detoxification and repair such as catalases, superoxide dismutases, glutathione peroxidases, and thioredoxins [ 76 , 80 , 81 , 83 ].…”