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Targeting zinc homeostasis to combat Aspergillus fumigatus infections
Aspergillus fumigatus is able to invade and grow in the lungs of immunosuppressed individuals and causes invasive pulmonary aspergillosis. The concentration of free zinc in living tissues is much lower than that required for optimal fungal growth in vitro because most of it is tightly bound to prote...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4343018/ https://www.ncbi.nlm.nih.gov/pubmed/25774155 http://dx.doi.org/10.3389/fmicb.2015.00160 |
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author | Vicentefranqueira, Rocío Amich, Jorge Laskaris, Paris Ibrahim-Granet, Oumaima Latgé, Jean P. Toledo, Héctor Leal, Fernando Calera, José A. |
author_facet | Vicentefranqueira, Rocío Amich, Jorge Laskaris, Paris Ibrahim-Granet, Oumaima Latgé, Jean P. Toledo, Héctor Leal, Fernando Calera, José A. |
author_sort | Vicentefranqueira, Rocío |
collection | PubMed |
description | Aspergillus fumigatus is able to invade and grow in the lungs of immunosuppressed individuals and causes invasive pulmonary aspergillosis. The concentration of free zinc in living tissues is much lower than that required for optimal fungal growth in vitro because most of it is tightly bound to proteins. To obtain efficiently zinc from a living host A. fumigatus uses the zinc transporters ZrfA, ZrfB, and ZrfC. The ZafA transcriptional regulator induces the expression of all these transporters and is essential for virulence. Thus, ZafA could be targeted therapeutically to inhibit fungal growth. The ZrfC transporter plays the major role in zinc acquisition from the host whereas ZrfA and ZrfB rather have a supplementary role to that of ZrfC. In addition, only ZrfC enables A. fumigatus to overcome the inhibitory effect of calprotectin, which is an antimicrobial Zn/Mn-chelating protein synthesized and released by neutrophils within the fungal abscesses of immunosuppressed non-leucopenic animals. Hence, fungal survival in these animals would be undermined upon blocking therapeutically the function of ZrfC. Therefore, both ZafA and ZrfC have emerged as promising targets for the discovery of new antifungals to treat Aspergillus infections. |
format | Online Article Text |
id | pubmed-4343018 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-43430182015-03-13 Targeting zinc homeostasis to combat Aspergillus fumigatus infections Vicentefranqueira, Rocío Amich, Jorge Laskaris, Paris Ibrahim-Granet, Oumaima Latgé, Jean P. Toledo, Héctor Leal, Fernando Calera, José A. Front Microbiol Microbiology Aspergillus fumigatus is able to invade and grow in the lungs of immunosuppressed individuals and causes invasive pulmonary aspergillosis. The concentration of free zinc in living tissues is much lower than that required for optimal fungal growth in vitro because most of it is tightly bound to proteins. To obtain efficiently zinc from a living host A. fumigatus uses the zinc transporters ZrfA, ZrfB, and ZrfC. The ZafA transcriptional regulator induces the expression of all these transporters and is essential for virulence. Thus, ZafA could be targeted therapeutically to inhibit fungal growth. The ZrfC transporter plays the major role in zinc acquisition from the host whereas ZrfA and ZrfB rather have a supplementary role to that of ZrfC. In addition, only ZrfC enables A. fumigatus to overcome the inhibitory effect of calprotectin, which is an antimicrobial Zn/Mn-chelating protein synthesized and released by neutrophils within the fungal abscesses of immunosuppressed non-leucopenic animals. Hence, fungal survival in these animals would be undermined upon blocking therapeutically the function of ZrfC. Therefore, both ZafA and ZrfC have emerged as promising targets for the discovery of new antifungals to treat Aspergillus infections. Frontiers Media S.A. 2015-02-27 /pmc/articles/PMC4343018/ /pubmed/25774155 http://dx.doi.org/10.3389/fmicb.2015.00160 Text en Copyright © 2015 Vicentefranqueira, Amich, Laskaris, Ibrahim-Granet, Latgé, Toledo, Leal and Calera. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Vicentefranqueira, Rocío Amich, Jorge Laskaris, Paris Ibrahim-Granet, Oumaima Latgé, Jean P. Toledo, Héctor Leal, Fernando Calera, José A. Targeting zinc homeostasis to combat Aspergillus fumigatus infections |
title | Targeting zinc homeostasis to combat Aspergillus fumigatus infections |
title_full | Targeting zinc homeostasis to combat Aspergillus fumigatus infections |
title_fullStr | Targeting zinc homeostasis to combat Aspergillus fumigatus infections |
title_full_unstemmed | Targeting zinc homeostasis to combat Aspergillus fumigatus infections |
title_short | Targeting zinc homeostasis to combat Aspergillus fumigatus infections |
title_sort | targeting zinc homeostasis to combat aspergillus fumigatus infections |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4343018/ https://www.ncbi.nlm.nih.gov/pubmed/25774155 http://dx.doi.org/10.3389/fmicb.2015.00160 |
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