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Emerging Prospects for Combating Fungal Infections by Targeting Phosphatidylinositol Transfer Proteins

The emergence of fungal “superbugs” resistant to the limited cohort of anti-fungal agents available to clinicians is eroding our ability to effectively treat infections by these virulent pathogens. As the threat of fungal infection is escalating worldwide, this dwindling response capacity is fueling...

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Detalles Bibliográficos
Autores principales: Khan, Danish, Nile, Aaron H., Tripathi, Ashutosh, Bankaitis, Vytas A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269425/
https://www.ncbi.nlm.nih.gov/pubmed/34201733
http://dx.doi.org/10.3390/ijms22136754
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author Khan, Danish
Nile, Aaron H.
Tripathi, Ashutosh
Bankaitis, Vytas A.
author_facet Khan, Danish
Nile, Aaron H.
Tripathi, Ashutosh
Bankaitis, Vytas A.
author_sort Khan, Danish
collection PubMed
description The emergence of fungal “superbugs” resistant to the limited cohort of anti-fungal agents available to clinicians is eroding our ability to effectively treat infections by these virulent pathogens. As the threat of fungal infection is escalating worldwide, this dwindling response capacity is fueling concerns of impending global health emergencies. These developments underscore the urgent need for new classes of anti-fungal drugs and, therefore, the identification of new targets. Phosphoinositide signaling does not immediately appear to offer attractive targets due to its evolutionary conservation across the Eukaryota. However, recent evidence argues otherwise. Herein, we discuss the evidence identifying Sec14-like phosphatidylinositol transfer proteins (PITPs) as unexplored portals through which phosphoinositide signaling in virulent fungi can be chemically disrupted with exquisite selectivity. Recent identification of lead compounds that target fungal Sec14 proteins, derived from several distinct chemical scaffolds, reveals exciting inroads into the rational design of next generation Sec14 inhibitors. Development of appropriately refined next generation Sec14-directed inhibitors promises to expand the chemical weaponry available for deployment in the shifting field of engagement between fungal pathogens and their human hosts.
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spelling pubmed-82694252021-07-10 Emerging Prospects for Combating Fungal Infections by Targeting Phosphatidylinositol Transfer Proteins Khan, Danish Nile, Aaron H. Tripathi, Ashutosh Bankaitis, Vytas A. Int J Mol Sci Review The emergence of fungal “superbugs” resistant to the limited cohort of anti-fungal agents available to clinicians is eroding our ability to effectively treat infections by these virulent pathogens. As the threat of fungal infection is escalating worldwide, this dwindling response capacity is fueling concerns of impending global health emergencies. These developments underscore the urgent need for new classes of anti-fungal drugs and, therefore, the identification of new targets. Phosphoinositide signaling does not immediately appear to offer attractive targets due to its evolutionary conservation across the Eukaryota. However, recent evidence argues otherwise. Herein, we discuss the evidence identifying Sec14-like phosphatidylinositol transfer proteins (PITPs) as unexplored portals through which phosphoinositide signaling in virulent fungi can be chemically disrupted with exquisite selectivity. Recent identification of lead compounds that target fungal Sec14 proteins, derived from several distinct chemical scaffolds, reveals exciting inroads into the rational design of next generation Sec14 inhibitors. Development of appropriately refined next generation Sec14-directed inhibitors promises to expand the chemical weaponry available for deployment in the shifting field of engagement between fungal pathogens and their human hosts. MDPI 2021-06-23 /pmc/articles/PMC8269425/ /pubmed/34201733 http://dx.doi.org/10.3390/ijms22136754 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Khan, Danish
Nile, Aaron H.
Tripathi, Ashutosh
Bankaitis, Vytas A.
Emerging Prospects for Combating Fungal Infections by Targeting Phosphatidylinositol Transfer Proteins
title Emerging Prospects for Combating Fungal Infections by Targeting Phosphatidylinositol Transfer Proteins
title_full Emerging Prospects for Combating Fungal Infections by Targeting Phosphatidylinositol Transfer Proteins
title_fullStr Emerging Prospects for Combating Fungal Infections by Targeting Phosphatidylinositol Transfer Proteins
title_full_unstemmed Emerging Prospects for Combating Fungal Infections by Targeting Phosphatidylinositol Transfer Proteins
title_short Emerging Prospects for Combating Fungal Infections by Targeting Phosphatidylinositol Transfer Proteins
title_sort emerging prospects for combating fungal infections by targeting phosphatidylinositol transfer proteins
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269425/
https://www.ncbi.nlm.nih.gov/pubmed/34201733
http://dx.doi.org/10.3390/ijms22136754
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