Publicação
Expansion, functional diversification, and gene fusion events in the Ato protein family
| Resumo: | Candida albicans, a commensal opportunistic pathogen, exhibits remarkable metabolic flexibility and adaptability to environmental changes. In glucose-limited niches, it utilizes alternative carbon sources such as carboxylic acids, which may influence its pathogenicity. In Saccharomyces cerevisiae, the uptake of monocarboxylates occurs through regulated plasma membrane (PM) transport proteins, such as Ato1 (Ady2), which belongs to the Acetate Uptake Transporter (AceTr) family. In C. albicans, these proteins are notably expanded, consisting of ten Ato-like proteins (ATO1-ATO10), whose functions remain unknown. Here, we investigated the role of Ato proteins in carboxylic acid utilization by C. albicans using in-silico and functional analysis. Our data revealed that several C. albicans Atos retain conserved AceTr motifs but possess distinct structural features, including differences in pore radius and binding sites for acetate and lactate. Expression analysis revealed that Ato1, Ato2, Ato3, and Ato6 exhibit distinct cellular localization and expression levels on the plasma membrane, depending on the presence or absence of monocarboxylates. Remarkably, deletion of ATO1 impaired Ato2 and Ato3 expression and caused ER retention of a distinct form of Ato2, suggesting a central regulatory role for Ato1 in the Ato transport system. Finally, we identified a novel Ato-related protein family in vertebrates. This family has three consecutive 6-helix transport domains and a unique C-terminal fusion with Sua5/YciO/YrdC, an enzyme involved in tRNA modification. Overall, our data suggests that the Ato protein family might play a critical role in the utilization of acetic or lactic acids in C. albicans. It also proposes potential functional redundancy among its members, which may contribute to rapid environmental adaptation and pathogenicity. |
|---|---|
| Autores principais: | Ghasemi, Faezeh |
| Outros Autores: | Ataíde, Patrícia; Barata-Antunes, Cláudia; Pyrris, Yiannis; Alves, João; Fernandes, Vitor; Alves, Rosana; Gomes-Gonçalves, Alexandra; Casal, Margarida; Van Genechten, Wouter; Nysten, Jana; Brown, Alistair J. P.; Van Dijck, Patrick; Diallinas, George; Pittis, Alexandros A.; Soares Silva, Isabel; Paiva, Sandra |
| Assunto: | Candida albicans plasma membrane proteins carboxylic acids |
| Ano: | 2026 |
| País: | Portugal |
| Tipo de documento: | preprint |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1877776053365112832 |
|---|---|
| author | Ghasemi, Faezeh |
| author2 | Ataíde, Patrícia Barata-Antunes, Cláudia Pyrris, Yiannis Alves, João Fernandes, Vitor Alves, Rosana Gomes-Gonçalves, Alexandra Casal, Margarida Van Genechten, Wouter Nysten, Jana Brown, Alistair J. P. Van Dijck, Patrick Diallinas, George Pittis, Alexandros A. Soares Silva, Isabel Paiva, Sandra |
| author2_role | author author author author author author author author author author author author author author author author |
| author_facet | Ghasemi, Faezeh Ataíde, Patrícia Barata-Antunes, Cláudia Pyrris, Yiannis Alves, João Fernandes, Vitor Alves, Rosana Gomes-Gonçalves, Alexandra Casal, Margarida Van Genechten, Wouter Nysten, Jana Brown, Alistair J. P. Van Dijck, Patrick Diallinas, George Pittis, Alexandros A. Soares Silva, Isabel Paiva, Sandra |
| author_role | author |
| contributor_name_str_mv | Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Ghasemi, Faezeh\"},{\"Person.name\":\"Ataíde, Patrícia\"},{\"Person.name\":\"Barata-Antunes, Cláudia\"},{\"Person.name\":\"Pyrris, Yiannis\"},{\"Person.name\":\"Alves, João\"},{\"Person.name\":\"Fernandes, Vitor\"},{\"Person.name\":\"Alves, Rosana\"},{\"Person.name\":\"Gomes-Gonçalves, Alexandra\"},{\"Person.name\":\"Casal, Margarida\"},{\"Person.name\":\"Van Genechten, Wouter\"},{\"Person.name\":\"Nysten, Jana\"},{\"Person.name\":\"Brown, Alistair J. P.\"},{\"Person.name\":\"Van Dijck, Patrick\"},{\"Person.name\":\"Diallinas, George\"},{\"Person.name\":\"Pittis, Alexandros A.\"},{\"Person.name\":\"Soares Silva, Isabel\"},{\"Person.name\":\"Paiva, Sandra\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Ghasemi, Faezeh Ataíde, Patrícia Barata-Antunes, Cláudia Pyrris, Yiannis Alves, João Fernandes, Vitor Alves, Rosana Gomes-Gonçalves, Alexandra Casal, Margarida Van Genechten, Wouter Nysten, Jana Brown, Alistair J. P. Van Dijck, Patrick Diallinas, George Pittis, Alexandros A. Soares Silva, Isabel Paiva, Sandra |
| datacite.date.Accepted.fl_str_mv | 2026-10-01T00:00:00Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Candida albicans plasma membrane proteins carboxylic acids |
| datacite.titles.title.fl_str_mv | Expansion, functional diversification, and gene fusion events in the Ato protein family |
| dc.contributor.none.fl_str_mv | Universidade do Minho |
| dc.creator.none.fl_str_mv | Ghasemi, Faezeh Ataíde, Patrícia Barata-Antunes, Cláudia Pyrris, Yiannis Alves, João Fernandes, Vitor Alves, Rosana Gomes-Gonçalves, Alexandra Casal, Margarida Van Genechten, Wouter Nysten, Jana Brown, Alistair J. P. Van Dijck, Patrick Diallinas, George Pittis, Alexandros A. Soares Silva, Isabel Paiva, Sandra |
| dc.date.Accepted.fl_str_mv | 2026-10-01T00:00:00Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/100729 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Cold Spring Harbor Laboratory Press |
| dc.rights.cclincense.fl_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.rights.rights.copyright.fl_str_mv | openAccess |
| dc.subject.none.fl_str_mv | Candida albicans plasma membrane proteins carboxylic acids |
| dc.title.fl_str_mv | Expansion, functional diversification, and gene fusion events in the Ato protein family |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_816b |
| description | Candida albicans, a commensal opportunistic pathogen, exhibits remarkable metabolic flexibility and adaptability to environmental changes. In glucose-limited niches, it utilizes alternative carbon sources such as carboxylic acids, which may influence its pathogenicity. In Saccharomyces cerevisiae, the uptake of monocarboxylates occurs through regulated plasma membrane (PM) transport proteins, such as Ato1 (Ady2), which belongs to the Acetate Uptake Transporter (AceTr) family. In C. albicans, these proteins are notably expanded, consisting of ten Ato-like proteins (ATO1-ATO10), whose functions remain unknown. Here, we investigated the role of Ato proteins in carboxylic acid utilization by C. albicans using in-silico and functional analysis. Our data revealed that several C. albicans Atos retain conserved AceTr motifs but possess distinct structural features, including differences in pore radius and binding sites for acetate and lactate. Expression analysis revealed that Ato1, Ato2, Ato3, and Ato6 exhibit distinct cellular localization and expression levels on the plasma membrane, depending on the presence or absence of monocarboxylates. Remarkably, deletion of ATO1 impaired Ato2 and Ato3 expression and caused ER retention of a distinct form of Ato2, suggesting a central regulatory role for Ato1 in the Ato transport system. Finally, we identified a novel Ato-related protein family in vertebrates. This family has three consecutive 6-helix transport domains and a unique C-terminal fusion with Sua5/YciO/YrdC, an enzyme involved in tRNA modification. Overall, our data suggests that the Ato protein family might play a critical role in the utilization of acetic or lactic acids in C. albicans. It also proposes potential functional redundancy among its members, which may contribute to rapid environmental adaptation and pathogenicity. |
| dirty | 0 |
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| person_str_mv | Ghasemi, Faezeh Ataíde, Patrícia Barata-Antunes, Cláudia Pyrris, Yiannis Alves, João Fernandes, Vitor Alves, Rosana Gomes-Gonçalves, Alexandra Casal, Margarida Van Genechten, Wouter Nysten, Jana Brown, Alistair J. P. Van Dijck, Patrick Diallinas, George Pittis, Alexandros A. Soares Silva, Isabel Paiva, Sandra |
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| spelling | engCold Spring Harbor Laboratory PressporCandida albicans, a commensal opportunistic pathogen, exhibits remarkable metabolic flexibility and adaptability to environmental changes. In glucose-limited niches, it utilizes alternative carbon sources such as carboxylic acids, which may influence its pathogenicity. In Saccharomyces cerevisiae, the uptake of monocarboxylates occurs through regulated plasma membrane (PM) transport proteins, such as Ato1 (Ady2), which belongs to the Acetate Uptake Transporter (AceTr) family. In C. albicans, these proteins are notably expanded, consisting of ten Ato-like proteins (ATO1-ATO10), whose functions remain unknown. Here, we investigated the role of Ato proteins in carboxylic acid utilization by C. albicans using in-silico and functional analysis. Our data revealed that several C. albicans Atos retain conserved AceTr motifs but possess distinct structural features, including differences in pore radius and binding sites for acetate and lactate. Expression analysis revealed that Ato1, Ato2, Ato3, and Ato6 exhibit distinct cellular localization and expression levels on the plasma membrane, depending on the presence or absence of monocarboxylates. Remarkably, deletion of ATO1 impaired Ato2 and Ato3 expression and caused ER retention of a distinct form of Ato2, suggesting a central regulatory role for Ato1 in the Ato transport system. Finally, we identified a novel Ato-related protein family in vertebrates. This family has three consecutive 6-helix transport domains and a unique C-terminal fusion with Sua5/YciO/YrdC, an enzyme involved in tRNA modification. Overall, our data suggests that the Ato protein family might play a critical role in the utilization of acetic or lactic acids in C. albicans. It also proposes potential functional redundancy among its members, which may contribute to rapid environmental adaptation and pathogenicity.application/pdfengExpansion, functional diversification, and gene fusion events in the Ato protein familyGhasemi, FaezehAtaíde, PatríciaBarata-Antunes, CláudiaPyrris, YiannisAlves, JoãoFernandes, VitorAlves, RosanaGomes-Gonçalves, AlexandraCasal, MargaridaVan Genechten, WouterNysten, JanaBrown, Alistair J. P.Van Dijck, PatrickDiallinas, GeorgePittis, Alexandros A.Soares Silva, IsabelPaiva, SandraHostingInstitutionOrganizationalUniversidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptCITATIONGhasemi, F., Barata-Antunes, C., Pyrris, Y., Ataíde, P., Alves, J., Fernandes, V., Alves, R., Gomes-Gonçalves, A., Casal, M., Genechten, W. V., Nysten, J., Brown, A. J. P., Van Dijck, P., Diallinas, G., Pittis, A. A., Soares-Silva, I., & Paiva, S. (2025). Expansion, functional diversification and gene fusion events in the Ato protein family. bioRxiv. https://doi.org/10.1101/2025.05.26.656167v2DOIIsPartOf10.1101/2025.05.26.656167v2URLHasVersionhttps://www.biorxiv.org/content/10.1101/2025.05.26.656167v22026-102026-10-01T00:00:00ZHandlehttps://hdl.handle.net/1822/100729http://purl.org/coar/access_right/c_abf2open accessCandida albicansplasma membrane proteinscarboxylic acids1896343 bytesFundação para a Ciência e a Tecnologia, I.P.MetaFungal-Metabolism of carboxylic acids in Fungal Infections [PTDC/BIA-MIC/5246/2020]Concurso para Financiamento de Projetos de Investigação Científica e Desenvolvimento Tecnológico em Todos os Domínios Científicos - 2020https://hdl.handle.net/1822/100687PTDC/BIA-MIC/5246/2020Crossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a Tecnologia, I.P.Centre of Molecular and Environmental Biology [UID/04050/2025]Avaliação UID 2023/2024https://hdl.handle.net/1822/99756UID/04050/2025Crossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a Tecnologia, I.P.Metabolic Induced Regulation in Candida albicans pathogenesis: the role of carboxylic acids and carboxylate transporters [2021.08564.BD]https://hdl.handle.net/1822/1007192021.08564.BDCrossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a Tecnologia, I.P.The role of Nutrient Transporters in Candida albicans pathogenesis [2023.03135.BD]https://hdl.handle.net/1822/1007202023.03135.BDCrossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a Tecnologia, I.P.Yeast as a model system for the study carboxylic acid transporters [PD/BD/150584/2020]https://hdl.handle.net/1822/100728PD/BD/150584/2020Crossref Funder IDhttp://doi.org/10.13039/501100001871UK Research and InnovationImpact of fungal adaptation upon host recognition and pathogenesis [MR/M026663/2]MRChttps://hdl.handle.net/1822/100721MR/M026663/2Crossref Funder IDhttps://doi.org/10.13039/100014013Wellcome TrustFrom ‘molecular pattern’ to ligand structure and function – the origins of antifungal immunity [224323]Immune System in Health and Diseasehttps://hdl.handle.net/1822/100722224323Crossref Funder IDhttp://doi.org/10.13039/100010269UK Research and InnovationMRC Centre for Medical Mycology [MR/N006364/2]MRChttps://hdl.handle.net/1822/99564MR/N006364/2Crossref Funder IDhttps://doi.org/10.13039/100014013UK Research and InnovationMedical Research Council Centre for Medical Mycology [MR/V033417/1]MRChttps://hdl.handle.net/1822/99563MR/V033417/1Crossref Funder IDhttps://doi.org/10.13039/100014013other research producthttp://purl.org/coar/resource_type/c_816bpreprint2026-10http://creativecommons.org/licenses/by/4.0/openAccesshttp://purl.org/coar/access_right/c_abf2application/pdfhttps://repositorium.uminho.pt/bitstreams/0cfe9459-992b-4428-a4c1-446516080001/download |
| spellingShingle | Expansion, functional diversification, and gene fusion events in the Ato protein family Ghasemi, Faezeh Candida albicans plasma membrane proteins carboxylic acids |
| status | SINGLETON |
| subject.fl_str_mv | Candida albicans plasma membrane proteins carboxylic acids |
| title | Expansion, functional diversification, and gene fusion events in the Ato protein family |
| title_full | Expansion, functional diversification, and gene fusion events in the Ato protein family |
| title_fullStr | Expansion, functional diversification, and gene fusion events in the Ato protein family |
| title_full_unstemmed | Expansion, functional diversification, and gene fusion events in the Ato protein family |
| title_short | Expansion, functional diversification, and gene fusion events in the Ato protein family |
| title_sort | Expansion, functional diversification, and gene fusion events in the Ato protein family |
| topic | Candida albicans plasma membrane proteins carboxylic acids |
| topic_facet | Candida albicans plasma membrane proteins carboxylic acids |
| url | https://hdl.handle.net/1822/100729 |
| visible | 1 |