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

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 antifung...

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Detalles Bibliográficos
Autores principales: Hans, Sandeep, Fatima, Zeeshan, Ahmad, Aijaz, Hameed, Saif
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282612/
https://www.ncbi.nlm.nih.gov/pubmed/35834579
http://dx.doi.org/10.1371/journal.pone.0270676
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author Hans, Sandeep
Fatima, Zeeshan
Ahmad, Aijaz
Hameed, Saif
author_facet Hans, Sandeep
Fatima, Zeeshan
Ahmad, Aijaz
Hameed, Saif
author_sort Hans, Sandeep
collection PubMed
description 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.
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spelling pubmed-92826122022-07-15 Magnesium impairs Candida albicans immune evasion by reduced hyphal damage, enhanced β-glucan exposure and altered vacuole homeostasis Hans, Sandeep Fatima, Zeeshan Ahmad, Aijaz Hameed, Saif PLoS One Research Article 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. Public Library of Science 2022-07-14 /pmc/articles/PMC9282612/ /pubmed/35834579 http://dx.doi.org/10.1371/journal.pone.0270676 Text en © 2022 Hans et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Hans, Sandeep
Fatima, Zeeshan
Ahmad, Aijaz
Hameed, Saif
Magnesium impairs Candida albicans immune evasion by reduced hyphal damage, enhanced β-glucan exposure and altered vacuole homeostasis
title Magnesium impairs Candida albicans immune evasion by reduced hyphal damage, enhanced β-glucan exposure and altered vacuole homeostasis
title_full Magnesium impairs Candida albicans immune evasion by reduced hyphal damage, enhanced β-glucan exposure and altered vacuole homeostasis
title_fullStr Magnesium impairs Candida albicans immune evasion by reduced hyphal damage, enhanced β-glucan exposure and altered vacuole homeostasis
title_full_unstemmed Magnesium impairs Candida albicans immune evasion by reduced hyphal damage, enhanced β-glucan exposure and altered vacuole homeostasis
title_short Magnesium impairs Candida albicans immune evasion by reduced hyphal damage, enhanced β-glucan exposure and altered vacuole homeostasis
title_sort magnesium impairs candida albicans immune evasion by reduced hyphal damage, enhanced β-glucan exposure and altered vacuole homeostasis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9282612/
https://www.ncbi.nlm.nih.gov/pubmed/35834579
http://dx.doi.org/10.1371/journal.pone.0270676
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