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Potential Antifungal Targets for Aspergillus sp. from the Calcineurin and Heat Shock Protein Pathways
Aspergillus species, especially A. fumigatus, and to a lesser extent others (A. flavus, A. niger, A. terreus), although rarely pathogenic to healthy humans, can be very aggressive to immunocompromised patients (they are opportunistic pathogens). Although survival rates for such infections have impro...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9603945/ https://www.ncbi.nlm.nih.gov/pubmed/36293395 http://dx.doi.org/10.3390/ijms232012543 |
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author | Ancuceanu, Robert Hovaneț, Marilena Viorica Cojocaru-Toma, Maria Anghel, Adriana-Iuliana Dinu, Mihaela |
author_facet | Ancuceanu, Robert Hovaneț, Marilena Viorica Cojocaru-Toma, Maria Anghel, Adriana-Iuliana Dinu, Mihaela |
author_sort | Ancuceanu, Robert |
collection | PubMed |
description | Aspergillus species, especially A. fumigatus, and to a lesser extent others (A. flavus, A. niger, A. terreus), although rarely pathogenic to healthy humans, can be very aggressive to immunocompromised patients (they are opportunistic pathogens). Although survival rates for such infections have improved in recent decades following the introduction of azole derivatives, they remain a clinical challenge. The fact that current antifungals act as fungistatic rather than fungicide, that they have limited safety, and that resistance is becoming increasingly common make the need for new, more effective, and safer therapies to become more acute. Over the last decades, knowledge about the molecular biology of A. fumigatus and other Aspergillus species, and particularly of calcineurin, Hsp90, and their signaling pathway proteins, has progressed remarkably. Although calcineurin has attracted much interest, its adverse effects, particularly its immunosuppressive effects, make it less attractive than it might at first appear. The situation is not very different for Hsp90. Other proteins from their signaling pathways, such as protein kinases phosphorylating the four SPRR serine residues, CrzA, rcnA, pmcA-pmcC (particularly pmcC), rfeF, BAR adapter protein(s), the phkB histidine kinase, sskB MAP kinase kinase, zfpA, htfA, ctfA, SwoH (nucleoside diphosphate kinase), CchA, MidA, FKBP12, the K27 lysine position from Hsp90, PkcA, MpkA, RlmA, brlA, abaA, wetA, other heat shock proteins (Hsp70, Hsp40, Hsp12) currently appear promising and deserve further investigation as potential targets for antifungal drug development. |
format | Online Article Text |
id | pubmed-9603945 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96039452022-10-27 Potential Antifungal Targets for Aspergillus sp. from the Calcineurin and Heat Shock Protein Pathways Ancuceanu, Robert Hovaneț, Marilena Viorica Cojocaru-Toma, Maria Anghel, Adriana-Iuliana Dinu, Mihaela Int J Mol Sci Review Aspergillus species, especially A. fumigatus, and to a lesser extent others (A. flavus, A. niger, A. terreus), although rarely pathogenic to healthy humans, can be very aggressive to immunocompromised patients (they are opportunistic pathogens). Although survival rates for such infections have improved in recent decades following the introduction of azole derivatives, they remain a clinical challenge. The fact that current antifungals act as fungistatic rather than fungicide, that they have limited safety, and that resistance is becoming increasingly common make the need for new, more effective, and safer therapies to become more acute. Over the last decades, knowledge about the molecular biology of A. fumigatus and other Aspergillus species, and particularly of calcineurin, Hsp90, and their signaling pathway proteins, has progressed remarkably. Although calcineurin has attracted much interest, its adverse effects, particularly its immunosuppressive effects, make it less attractive than it might at first appear. The situation is not very different for Hsp90. Other proteins from their signaling pathways, such as protein kinases phosphorylating the four SPRR serine residues, CrzA, rcnA, pmcA-pmcC (particularly pmcC), rfeF, BAR adapter protein(s), the phkB histidine kinase, sskB MAP kinase kinase, zfpA, htfA, ctfA, SwoH (nucleoside diphosphate kinase), CchA, MidA, FKBP12, the K27 lysine position from Hsp90, PkcA, MpkA, RlmA, brlA, abaA, wetA, other heat shock proteins (Hsp70, Hsp40, Hsp12) currently appear promising and deserve further investigation as potential targets for antifungal drug development. MDPI 2022-10-19 /pmc/articles/PMC9603945/ /pubmed/36293395 http://dx.doi.org/10.3390/ijms232012543 Text en © 2022 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 Ancuceanu, Robert Hovaneț, Marilena Viorica Cojocaru-Toma, Maria Anghel, Adriana-Iuliana Dinu, Mihaela Potential Antifungal Targets for Aspergillus sp. from the Calcineurin and Heat Shock Protein Pathways |
title | Potential Antifungal Targets for Aspergillus sp. from the Calcineurin and Heat Shock Protein Pathways |
title_full | Potential Antifungal Targets for Aspergillus sp. from the Calcineurin and Heat Shock Protein Pathways |
title_fullStr | Potential Antifungal Targets for Aspergillus sp. from the Calcineurin and Heat Shock Protein Pathways |
title_full_unstemmed | Potential Antifungal Targets for Aspergillus sp. from the Calcineurin and Heat Shock Protein Pathways |
title_short | Potential Antifungal Targets for Aspergillus sp. from the Calcineurin and Heat Shock Protein Pathways |
title_sort | potential antifungal targets for aspergillus sp. from the calcineurin and heat shock protein pathways |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9603945/ https://www.ncbi.nlm.nih.gov/pubmed/36293395 http://dx.doi.org/10.3390/ijms232012543 |
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