Magnesium impairs Candida albicans immune evasion by reduced hyphal damage, enhanced β-glucan exposure and altered vacuole homeostasis

Abstract

With a limited arsenal of available antifungal drugs and drug-resistance emergence, strategies that seek to reduce Candida immune evasion and virulence could be a promising alternative option. Harnessing metal homeostasis against C. albicans has gained wide prominence nowadays as a feasible antifungal strategy. Herein, the effect of magnesium (Mg) deprivation on the immune evasion mechanisms of C. albicans is demonstrated. We studied host pathogen interaction by using the THP-1 cell line model and explored the avenue that macrophage-mediated killing was enhanced under Mg deprivation, leading to altered cytokine (TNFα, IL-6 and IL10) production and reduced pyroptosis. Insights into the mechanisms revealed that hyphal damage inside the macrophage was diminished under Mg deprivation. Additionally, Mg deprivation led to cell wall remodelling; leading to enhanced β-1,3-glucan exposure, crucial for immune recognition, along with concomitant alterations in chitin and mannan levels. Furthermore, vacuole homeostasis was disrupted under Mg deprivation, as revealed by abrogated morphology and defective acidification of the vacuole lumen. Together, we demonstrated that Mg deprivation affected immune evasion mechanisms by: reduced hyphal damage, enhanced β-1,3-glucan exposure and altered vacuole functioning. The study establishes that Mg availability is indispensable for successful C. albicans immune evasion and specific Mg dependent pathways could be targeted for therapy.

Biological and Physico-Chemical Properties of Composite Layers Based on Magnesium-Doped Hydroxyapatite in Chitosan Matrix

“…The strongest antifungal activity was noticed for the 30MgHApCh composite layers. These results are in good agreement with previously reported data and with the qualitative visualization by CLSM [ 8 , 22 , 32 , 33 , 52 , 53 , 54 ].…”

“…The obtained results highlighted that the MgHApCh composite layers could be taken into consideration for the development of future biocompatible devices with antifungal properties. Previous studies have reported that the biological properties of various materials and coatings could be correlated with the different intrinsic parameters of the samples and also with the biological environment they came into contact with [ 8 , 22 , 54 , 55 , 56 ]. More than that, the biological behavior of these composite layers could also be attributed to the synergistic interaction between the substrate and the composite material as well as to the physico-chemical properties of the coating material and its individual components.…”

Escherichia coli, but Not Staphylococcus aureus, Functions as a Chelating Agent That Exhibits Antifungal Activity against the Pathogenic Yeast Candida albicans

“…A recent report suggested that a lack of Mg affects the drug resistance mechanisms and immune evasion of C . albicans [ 55 ].…”

Hyphal Growth in Trichosporon asahii Is Accelerated by the Addition of Magnesium

“…Moreover, we found that the number of large vacuoles greater than 10 μm 2 in size, although not small vacuoles with a size of less than 10 μm 2 , increased when MgSO 4 was added to Sabouraud medium, thereby indicating that an increase in Mg 2+ might induce the fusion of small vacuoles. These observations may indicate the opposite effect of magnesium deprivation in C. albicans , in which vacuolar homeostasis was found to be abrogated by disrupting morphology and acidification ( 66 ). In C. albicans , FM4-64 has been shown to be localized to the vacuolar lumen and diffusely distributed under conditions of magnesium deprivation ( 66 ).…”

“…These observations may indicate the opposite effect of magnesium deprivation in C. albicans , in which vacuolar homeostasis was found to be abrogated by disrupting morphology and acidification ( 66 ). In C. albicans , FM4-64 has been shown to be localized to the vacuolar lumen and diffusely distributed under conditions of magnesium deprivation ( 66 ). Consequently, uptake of Mg 2+ may enhance vacuolar homeostasis and promote hyphal growth.…”