Lactic Acid Influences Iron Assimilation by a Fungal Pathogen via the Iron Reductive Uptake Pathway

Candida albicans is a fungal commensal of humans that often causes mucosal infections in otherwise healthy individuals and also serious infections in immunocompromised patients. The capacity of this fungus to colonize and cause disease relies on its ability to grow within the host, adapting to vario...

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Autores: Gomes-Gonçalves, Alexandra|||0000-0003-4595-5575, Van Genechten, Wouter, Ataíde, Patrícia, Barata-Antunes, Cláudia, Ghasemi, Faezeh, Casal, Margarida, Teixeira, Miguel C., Ariño Carmona, Joaquín|||0000-0002-6774-2987, Brown, Alistair J. P., Van Dijck, Patrick, Paiva, Sandra
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:dnet:uabarcelona_::fc5f1efef9d3a5b6766ba5a187fd6007
Acceso en línea:https://ddd.uab.cat/record/326518
https://dx.doi.org/urn:doi:10.1002/mbo3.70167
Access Level:acceso abierto
Palabra clave:Candida albicans
Fungal pathogenesis
Iron homeostasis
Lactate
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spelling Lactic Acid Influences Iron Assimilation by a Fungal Pathogen via the Iron Reductive Uptake PathwayGomes-Gonçalves, Alexandra|||0000-0003-4595-5575Van Genechten, WouterAtaíde, PatríciaBarata-Antunes, CláudiaGhasemi, FaezehCasal, MargaridaTeixeira, Miguel C.Ariño Carmona, Joaquín|||0000-0002-6774-2987Brown, Alistair J. P.Van Dijck, PatrickPaiva, SandraCandida albicansFungal pathogenesisIron homeostasisLactateCandida albicans is a fungal commensal of humans that often causes mucosal infections in otherwise healthy individuals and also serious infections in immunocompromised patients. The capacity of this fungus to colonize and cause disease relies on its ability to grow within the host, adapting to various nutrient restrictions and physicochemical conditions. The presence of alternative carbon sources, such as the lactate produced by the local microbiota, influences C. albicans antifungal drug resistance and immune evasion. In this study, we used genome-wide transcriptomic analysis to investigate the effect of lactate exposure upon metabolic rewiring. We provide evidence that C. albicans cells respond to growth in the presence of lactate at pH 5 by regulating genes encoding micronutrient transporters, notably iron transporters. More specifically, lactate triggers the downregulation of genes on the reductive iron uptake pathway, inferring a diminished requirement for high-affinity iron uptake. This is supported by the observation that lactate promotes the intracellular accumulation of iron by C. albicans cells. Lactate even enhances the growth of iron-transport defective C. albicans cells under iron-limited conditions. Lactate is known to activate protein kinase A (PKA) signaling. However, lactate-induced iron assimilation is PKA-independent. This study provides new insights into the role of lactate in iron homeostasis-two important factors that promote C. albicans virulence in the mammalian host, where nutritional immunity is a key antimicrobial strategy. Lactate modulates iron homeostasis in Candida albicans by repressing the reductive iron uptake pathway, reducing reliance on high-affinity iron transport. This process promotes intracellular iron accumulation and enhances growth, even in iron-transport-deficient strains under iron-limited conditions. Notably, this effect is independent of protein kinase A signaling, despite lactate's known activation of this pathway. These findings illustrate lactate's role in iron homeostasis, emphasizing its contribution to C. albicans adaptation and virulence in the host environment.Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular 22025-01-0120252025-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/326518https://dx.doi.org/urn:doi:10.1002/mbo3.70167reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2020-113319RB-I00Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 PID2023-150535OB-I00open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:dnet:uabarcelona_::fc5f1efef9d3a5b6766ba5a187fd60072026-06-06T12:50:31Z
dc.title.none.fl_str_mv Lactic Acid Influences Iron Assimilation by a Fungal Pathogen via the Iron Reductive Uptake Pathway
title Lactic Acid Influences Iron Assimilation by a Fungal Pathogen via the Iron Reductive Uptake Pathway
spellingShingle Lactic Acid Influences Iron Assimilation by a Fungal Pathogen via the Iron Reductive Uptake Pathway
Gomes-Gonçalves, Alexandra|||0000-0003-4595-5575
Candida albicans
Fungal pathogenesis
Iron homeostasis
Lactate
title_short Lactic Acid Influences Iron Assimilation by a Fungal Pathogen via the Iron Reductive Uptake Pathway
title_full Lactic Acid Influences Iron Assimilation by a Fungal Pathogen via the Iron Reductive Uptake Pathway
title_fullStr Lactic Acid Influences Iron Assimilation by a Fungal Pathogen via the Iron Reductive Uptake Pathway
title_full_unstemmed Lactic Acid Influences Iron Assimilation by a Fungal Pathogen via the Iron Reductive Uptake Pathway
title_sort Lactic Acid Influences Iron Assimilation by a Fungal Pathogen via the Iron Reductive Uptake Pathway
dc.creator.none.fl_str_mv Gomes-Gonçalves, Alexandra|||0000-0003-4595-5575
Van Genechten, Wouter
Ataíde, Patrícia
Barata-Antunes, Cláudia
Ghasemi, Faezeh
Casal, Margarida
Teixeira, Miguel C.
Ariño Carmona, Joaquín|||0000-0002-6774-2987
Brown, Alistair J. P.
Van Dijck, Patrick
Paiva, Sandra
author Gomes-Gonçalves, Alexandra|||0000-0003-4595-5575
author_facet Gomes-Gonçalves, Alexandra|||0000-0003-4595-5575
Van Genechten, Wouter
Ataíde, Patrícia
Barata-Antunes, Cláudia
Ghasemi, Faezeh
Casal, Margarida
Teixeira, Miguel C.
Ariño Carmona, Joaquín|||0000-0002-6774-2987
Brown, Alistair J. P.
Van Dijck, Patrick
Paiva, Sandra
author_role author
author2 Van Genechten, Wouter
Ataíde, Patrícia
Barata-Antunes, Cláudia
Ghasemi, Faezeh
Casal, Margarida
Teixeira, Miguel C.
Ariño Carmona, Joaquín|||0000-0002-6774-2987
Brown, Alistair J. P.
Van Dijck, Patrick
Paiva, Sandra
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular
dc.subject.none.fl_str_mv Candida albicans
Fungal pathogenesis
Iron homeostasis
Lactate
topic Candida albicans
Fungal pathogenesis
Iron homeostasis
Lactate
description Candida albicans is a fungal commensal of humans that often causes mucosal infections in otherwise healthy individuals and also serious infections in immunocompromised patients. The capacity of this fungus to colonize and cause disease relies on its ability to grow within the host, adapting to various nutrient restrictions and physicochemical conditions. The presence of alternative carbon sources, such as the lactate produced by the local microbiota, influences C. albicans antifungal drug resistance and immune evasion. In this study, we used genome-wide transcriptomic analysis to investigate the effect of lactate exposure upon metabolic rewiring. We provide evidence that C. albicans cells respond to growth in the presence of lactate at pH 5 by regulating genes encoding micronutrient transporters, notably iron transporters. More specifically, lactate triggers the downregulation of genes on the reductive iron uptake pathway, inferring a diminished requirement for high-affinity iron uptake. This is supported by the observation that lactate promotes the intracellular accumulation of iron by C. albicans cells. Lactate even enhances the growth of iron-transport defective C. albicans cells under iron-limited conditions. Lactate is known to activate protein kinase A (PKA) signaling. However, lactate-induced iron assimilation is PKA-independent. This study provides new insights into the role of lactate in iron homeostasis-two important factors that promote C. albicans virulence in the mammalian host, where nutritional immunity is a key antimicrobial strategy. Lactate modulates iron homeostasis in Candida albicans by repressing the reductive iron uptake pathway, reducing reliance on high-affinity iron transport. This process promotes intracellular iron accumulation and enhances growth, even in iron-transport-deficient strains under iron-limited conditions. Notably, this effect is independent of protein kinase A signaling, despite lactate's known activation of this pathway. These findings illustrate lactate's role in iron homeostasis, emphasizing its contribution to C. albicans adaptation and virulence in the host environment.
publishDate 2025
dc.date.none.fl_str_mv 2
2025-01-01
2025
2025-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/326518
https://dx.doi.org/urn:doi:10.1002/mbo3.70167
url https://ddd.uab.cat/record/326518
https://dx.doi.org/urn:doi:10.1002/mbo3.70167
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 PID2020-113319RB-I00
Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 PID2023-150535OB-I00
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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