Publicação
Application of antisense therapy to control Nakaseomyces glabratus infections
| Resumo: | Canclicla infections affect billions of people worlclwicle, with high morbidity ancl mortality rates (40-60CX,) [l] ancl require long hospital stays ancl increase healthcare costs, which places a significant socio-economic burclen on the economy [2]. Canclicla glabrata (now reclassified as Nakaseomyces glabratus) poses a significant clinical challenge, clue to its increasing levels of resistance to conventional anti fungal therapies, particularly azoles [3]. In this context, antisense therapy (AST) has emergecl as a promising approach in recent clecacles, demonstrating significant potential not only for treating human genetic diseases but also for combating infections [4]. This work aims to clevelop antisense oligonucleoticles (ASOs) targeting resistance-associated genes in N. glabratus, with the objective of restoring susceptibility to conventional antifungal treatments. Specifically, an ASO was clesignecl to target the PDRl gene, a crucial regulator of efflux pump expression ancl membrane permeability, which plays a significant role in antifungal resistance. The therapeutic potential of the anti-PDRl ASO was initially assessed in vitro to determine its effectiveness in reducing gene expression ancl enhancing susceptibility to fluconazole. To enhance bioavailability ancl stability within a living organism, the anti-PDRl ASO was encapsulated in lipicl nanoparticles (LPXs-ASOs), a delivery approach previously clemonstratecl to be effective for other Canclicla species [S]. Subsequently, the in vivo efficacy of the encapsulated ASO was valiclatecl using Galleria mellonella larvae as the moclel organism [6]. In vitro results showecl that the anti-PDRJ ASO was able to effectively recluce the PDRI expression by 40%, even uncler fluconazole-inclucecl conclitions. Aclclitionally, the ASO enhanced the growth inhibition of N. gla/Jratus by at least 20%, both in the presence ancl absence of fluconazole, ancl when ASO was free or encapsulatecl in LPXs. In vivo, the administration of LPXs-ASO significantly enhanced the survival rate ancl health inclex of the infectecl Galleria mellonella larvae moclel by approximately 20'Yc,. Overall, these finclings highlight AST as a promising strategy to resensitize N. gla/Jratus to traditional antifungal clrugs, provicling a new way of aclclressing the urgent issue of antifungal resistance. |
|---|---|
| Autores principais: | Serra, Patrícia |
| Outros Autores: | Gonçalves, Bruna; Henriques, Mariana; Castro, Joana; Araújo, Daniela; Silva, Sónia Carina |
| Assunto: | Canc/icla infections Antifungal resistance Antisense oligonucleotides Lipid nanoparticles |
| Ano: | 2025 |
| País: | Portugal |
| Tipo de documento: | outro |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1867439035601911808 |
|---|---|
| author | Serra, Patrícia |
| author2 | Gonçalves, Bruna Henriques, Mariana Castro, Joana Araújo, Daniela Silva, Sónia Carina |
| author2_role | author author author author author |
| author_facet | Serra, Patrícia Gonçalves, Bruna Henriques, Mariana Castro, Joana Araújo, Daniela Silva, Sónia Carina |
| author_role | author |
| contributor_name_str_mv | RepositóriUM - Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Serra, Patrícia\"},{\"Person.name\":\"Gonçalves, Bruna\"},{\"Person.name\":\"Henriques, Mariana\"},{\"Person.name\":\"Castro, Joana\"},{\"Person.name\":\"Araújo, Daniela\"},{\"Person.name\":\"Silva, Sónia Carina\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | RepositóriUM - Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Serra, Patrícia Gonçalves, Bruna Henriques, Mariana Castro, Joana Araújo, Daniela Silva, Sónia Carina |
| datacite.date.Accepted.fl_str_mv | 2025-05-30T00:00:00Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Canc/icla infections Antifungal resistance Antisense oligonucleotides Lipid nanoparticles |
| datacite.titles.title.fl_str_mv | Application of antisense therapy to control Nakaseomyces glabratus infections |
| dc.contributor.none.fl_str_mv | RepositóriUM - Universidade do Minho |
| dc.creator.none.fl_str_mv | Serra, Patrícia Gonçalves, Bruna Henriques, Mariana Castro, Joana Araújo, Daniela Silva, Sónia Carina |
| dc.date.Accepted.fl_str_mv | 2025-05-30T00:00:00Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/97494 |
| dc.language.none.fl_str_mv | eng |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Canc/icla infections Antifungal resistance Antisense oligonucleotides Lipid nanoparticles |
| dc.title.fl_str_mv | Application of antisense therapy to control Nakaseomyces glabratus infections |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_1843 |
| description | Canclicla infections affect billions of people worlclwicle, with high morbidity ancl mortality rates (40-60CX,) [l] ancl require long hospital stays ancl increase healthcare costs, which places a significant socio-economic burclen on the economy [2]. Canclicla glabrata (now reclassified as Nakaseomyces glabratus) poses a significant clinical challenge, clue to its increasing levels of resistance to conventional anti fungal therapies, particularly azoles [3]. In this context, antisense therapy (AST) has emergecl as a promising approach in recent clecacles, demonstrating significant potential not only for treating human genetic diseases but also for combating infections [4]. This work aims to clevelop antisense oligonucleoticles (ASOs) targeting resistance-associated genes in N. glabratus, with the objective of restoring susceptibility to conventional antifungal treatments. Specifically, an ASO was clesignecl to target the PDRl gene, a crucial regulator of efflux pump expression ancl membrane permeability, which plays a significant role in antifungal resistance. The therapeutic potential of the anti-PDRl ASO was initially assessed in vitro to determine its effectiveness in reducing gene expression ancl enhancing susceptibility to fluconazole. To enhance bioavailability ancl stability within a living organism, the anti-PDRl ASO was encapsulated in lipicl nanoparticles (LPXs-ASOs), a delivery approach previously clemonstratecl to be effective for other Canclicla species [S]. Subsequently, the in vivo efficacy of the encapsulated ASO was valiclatecl using Galleria mellonella larvae as the moclel organism [6]. In vitro results showecl that the anti-PDRJ ASO was able to effectively recluce the PDRI expression by 40%, even uncler fluconazole-inclucecl conclitions. Aclclitionally, the ASO enhanced the growth inhibition of N. gla/Jratus by at least 20%, both in the presence ancl absence of fluconazole, ancl when ASO was free or encapsulatecl in LPXs. In vivo, the administration of LPXs-ASO significantly enhanced the survival rate ancl health inclex of the infectecl Galleria mellonella larvae moclel by approximately 20'Yc,. Overall, these finclings highlight AST as a promising strategy to resensitize N. gla/Jratus to traditional antifungal clrugs, provicling a new way of aclclressing the urgent issue of antifungal resistance. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | other |
| fulltext.url.fl_str_mv | https://repositorium.uminho.pt/bitstreams/a57f840e-c0b9-4630-b8bf-eb318b38a46b/download |
| id | rum_4e5fb01c4045f2c048708ecbbf640b2d |
| identifier.url.fl_str_mv | https://hdl.handle.net/1822/97494 |
| instacron_str | repositorium |
| institution | Universidade do Minho |
| instname_str | Universidade do Minho |
| language | eng |
| network_acronym_str | rum |
| network_name_str | RepositóriUM - Universidade do Minho |
| oai_identifier_str | oai:repositorium.uminho.pt:1822/97494 |
| organization_str_mv | urn:organizationAcronym:repositorium |
| person_str_mv | Serra, Patrícia Gonçalves, Bruna Henriques, Mariana Castro, Joana Araújo, Daniela Silva, Sónia Carina |
| publishDate | 2025 |
| reponame_str | RepositóriUM - Universidade do Minho |
| repository_id_str | urn:repositoryAcronym:rum |
| service_str_mv | urn:repositoryAcronym:rum |
| spelling | engporCanclicla infections affect billions of people worlclwicle, with high morbidity ancl mortality rates (40-60CX,) [l] ancl require long hospital stays ancl increase healthcare costs, which places a significant socio-economic burclen on the economy [2]. Canclicla glabrata (now reclassified as Nakaseomyces glabratus) poses a significant clinical challenge, clue to its increasing levels of resistance to conventional anti fungal therapies, particularly azoles [3]. In this context, antisense therapy (AST) has emergecl as a promising approach in recent clecacles, demonstrating significant potential not only for treating human genetic diseases but also for combating infections [4]. This work aims to clevelop antisense oligonucleoticles (ASOs) targeting resistance-associated genes in N. glabratus, with the objective of restoring susceptibility to conventional antifungal treatments. Specifically, an ASO was clesignecl to target the PDRl gene, a crucial regulator of efflux pump expression ancl membrane permeability, which plays a significant role in antifungal resistance. The therapeutic potential of the anti-PDRl ASO was initially assessed in vitro to determine its effectiveness in reducing gene expression ancl enhancing susceptibility to fluconazole. To enhance bioavailability ancl stability within a living organism, the anti-PDRl ASO was encapsulated in lipicl nanoparticles (LPXs-ASOs), a delivery approach previously clemonstratecl to be effective for other Canclicla species [S]. Subsequently, the in vivo efficacy of the encapsulated ASO was valiclatecl using Galleria mellonella larvae as the moclel organism [6]. In vitro results showecl that the anti-PDRJ ASO was able to effectively recluce the PDRI expression by 40%, even uncler fluconazole-inclucecl conclitions. Aclclitionally, the ASO enhanced the growth inhibition of N. gla/Jratus by at least 20%, both in the presence ancl absence of fluconazole, ancl when ASO was free or encapsulatecl in LPXs. In vivo, the administration of LPXs-ASO significantly enhanced the survival rate ancl health inclex of the infectecl Galleria mellonella larvae moclel by approximately 20'Yc,. Overall, these finclings highlight AST as a promising strategy to resensitize N. gla/Jratus to traditional antifungal clrugs, provicling a new way of aclclressing the urgent issue of antifungal resistance.application/pdfengApplication of antisense therapy to control Nakaseomyces glabratus infectionsSerra, PatríciaGonçalves, BrunaHenriques, MarianaCastro, JoanaAraújo, DanielaSilva, Sónia CarinaHostingInstitutionOrganizationalRepositóriUM - Universidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptCITATIONSerra, Patrícia; Gonçalves, Bruna; Henriques, Mariana; Castro, Joana; Araújo, Daniela; Silva, Sónia Carina, Application of antisense therapy to control Nakaseomyces glabratus infections. 7EBTM - 7th Meeting on Medicinal Biotechnology & 3rd Congress on Mediconal Biotechnology. Porto, Portugal, May 30, 10, 2025.2025-05-302025-10-13T10:58:46Z2025-05-30T00:00:00ZHandlehttps://hdl.handle.net/1822/97494http://purl.org/coar/access_right/c_abf2open accessCanc/icla infectionsAntifungal resistanceAntisense oligonucleotidesLipid nanoparticles381152 bytesother research producthttp://purl.org/coar/resource_type/c_1843otherhttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorium.uminho.pt/bitstreams/a57f840e-c0b9-4630-b8bf-eb318b38a46b/download |
| spellingShingle | Application of antisense therapy to control Nakaseomyces glabratus infections Serra, Patrícia Canc/icla infections Antifungal resistance Antisense oligonucleotides Lipid nanoparticles |
| status | SINGLETON |
| subject.fl_str_mv | Canc/icla infections Antifungal resistance Antisense oligonucleotides Lipid nanoparticles |
| title | Application of antisense therapy to control Nakaseomyces glabratus infections |
| title_full | Application of antisense therapy to control Nakaseomyces glabratus infections |
| title_fullStr | Application of antisense therapy to control Nakaseomyces glabratus infections |
| title_full_unstemmed | Application of antisense therapy to control Nakaseomyces glabratus infections |
| title_short | Application of antisense therapy to control Nakaseomyces glabratus infections |
| title_sort | Application of antisense therapy to control Nakaseomyces glabratus infections |
| topic | Canc/icla infections Antifungal resistance Antisense oligonucleotides Lipid nanoparticles |
| topic_facet | Canc/icla infections Antifungal resistance Antisense oligonucleotides Lipid nanoparticles |
| url | https://hdl.handle.net/1822/97494 |
| visible | 1 |