Pathogenicity and resistance to antifungals-fungicides in Fusarium and Neocosmospora A One health approach
The primary objective of this doctoral thesis was to determine the presence of Fusarium and Neocosmospora in humans, animals, and plants through a One Health approach. To achieve this, we conducted phenotypic and molecular studies on samples obtained from various environments and human strains in Co...
- Autores:
-
Sáenz Moncaleano, Valeri Andrea
- Tipo de recurso:
- Doctoral thesis
- Fecha de publicación:
- 2024
- Institución:
- Universidad de los Andes
- Repositorio:
- Séneca: repositorio Uniandes
- Idioma:
- eng
- OAI Identifier:
- oai:repositorio.uniandes.edu.co:1992/74402
- Acceso en línea:
- https://hdl.handle.net/1992/74402
- Palabra clave:
- Fusarium
Neocosmospora
One health
Sea turtle Egg Fusariosis
Antifungal
Fungicide
Biología
- Rights
- embargoedAccess
- License
- Attribution-NonCommercial-NoDerivatives 4.0 International
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dc.title.eng.fl_str_mv |
Pathogenicity and resistance to antifungals-fungicides in Fusarium and Neocosmospora A One health approach |
dc.title.alternative.spa.fl_str_mv |
Estudio de la patogenicidad y resistencia a antifúngicos /fungicidas en Fusarium y Neocosmospora: Una aproximación desde la iniciativa One Health |
title |
Pathogenicity and resistance to antifungals-fungicides in Fusarium and Neocosmospora A One health approach |
spellingShingle |
Pathogenicity and resistance to antifungals-fungicides in Fusarium and Neocosmospora A One health approach Fusarium Neocosmospora One health Sea turtle Egg Fusariosis Antifungal Fungicide Biología |
title_short |
Pathogenicity and resistance to antifungals-fungicides in Fusarium and Neocosmospora A One health approach |
title_full |
Pathogenicity and resistance to antifungals-fungicides in Fusarium and Neocosmospora A One health approach |
title_fullStr |
Pathogenicity and resistance to antifungals-fungicides in Fusarium and Neocosmospora A One health approach |
title_full_unstemmed |
Pathogenicity and resistance to antifungals-fungicides in Fusarium and Neocosmospora A One health approach |
title_sort |
Pathogenicity and resistance to antifungals-fungicides in Fusarium and Neocosmospora A One health approach |
dc.creator.fl_str_mv |
Sáenz Moncaleano, Valeri Andrea |
dc.contributor.advisor.none.fl_str_mv |
Celis Ramírez, Adriana Marcela |
dc.contributor.author.none.fl_str_mv |
Sáenz Moncaleano, Valeri Andrea |
dc.contributor.jury.none.fl_str_mv |
Jiménez Alzate, María del Pilar Bernal Giraldo, Adriana Jimena |
dc.contributor.researchgroup.none.fl_str_mv |
Facultad de Ciencias::Grupo de Investigación Celular y Molecular de Microorganismos Patógenos (Cemop) |
dc.subject.keyword.eng.fl_str_mv |
Fusarium Neocosmospora One health Sea turtle Egg Fusariosis Antifungal Fungicide |
topic |
Fusarium Neocosmospora One health Sea turtle Egg Fusariosis Antifungal Fungicide Biología |
dc.subject.themes.none.fl_str_mv |
Biología |
description |
The primary objective of this doctoral thesis was to determine the presence of Fusarium and Neocosmospora in humans, animals, and plants through a One Health approach. To achieve this, we conducted phenotypic and molecular studies on samples obtained from various environments and human strains in Colombia to identify Fusarium or Neocosmospora. Our research revealed that Neocosmospora keratoplastica and Neocosmospora falciformis are prevalent in samples collected from humans, animals, and the environment (soil and sand). Notably, we describe Sea Turtle Egg Fusariosis (STEF) in sea turtles in Colombia for the first time. Furthermore, to find differences in how Fusarium/Neocosmospora interacts with hosts, we employed a Galleria mellonella animal model. We inoculated the larvae with clinical, animal, and environmental samples to carry out this experiment. We observed similar effects on mortality when the larvae were exposed to 1.5x106 UCF / ml of inoculum and incubated in a maintained incubation at 25 ° C. Also, it was observed that human, animal, and environmental samples can induce mortality in larvae at 37°C. Moreover, we determined the in vitro susceptibility profile of 52 isolates towards antifungal and fungicides. Our findings confirmed high Minimum Inhibitory Concentrations (MICs) to itraconazole, posaconazole, propiconazole, tebuconazole, and difenoconazole. However, amphotericin B and voriconazole showed susceptibility in most of the isolates. Subsequently, we aimed to investigate the antifungal effectiveness of molecules involved in Protein Kinase signaling pathways against Fusarium/Neocosmospora clinical isolates (n=12). To do this, we performed an in vitro test using four different inhibitors: the Pkc1 inhibitor (NPC15437), the p38 MAPK inhibitor (SKF 86002), the human Hsp90-Cdc37 inhibitor (Celastrol), and the antiparasitic drug Miltefosine. Our results indicate that the PKC1 inhibitor (NPC15437) and Miltefosine have promising antifungal activity. Finally, we address the challenges of diagnosing fungal keratitis in clinical and microbiologic settings. This was achieved through a survey of healthcare workers and collaboration with ophthalmologists, clinical microbiologists, and biodesigners to perform the design drafts and initial sketches of a medical device for corneal scraping. |
publishDate |
2024 |
dc.date.accessioned.none.fl_str_mv |
2024-06-27T18:25:09Z |
dc.date.issued.none.fl_str_mv |
2024-06-05 |
dc.date.accepted.none.fl_str_mv |
2024-06-27 |
dc.date.available.none.fl_str_mv |
2027-06-27 |
dc.type.none.fl_str_mv |
Trabajo de grado - Doctorado |
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info:eu-repo/semantics/doctoralThesis |
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https://hdl.handle.net/1992/74402 |
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eng |
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eng |
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Attribution-NonCommercial-NoDerivatives 4.0 International |
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http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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236 páginas |
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application/pdf |
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Universidad de los Andes |
dc.publisher.program.none.fl_str_mv |
Doctorado en Ciencias - Biología |
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Facultad de Ciencias |
dc.publisher.department.none.fl_str_mv |
Departamento de Ciencias Biológicas |
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Universidad de los Andes |
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Universidad de los Andes |
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Celis Ramírez, Adriana Marcelavirtual::18411-1Sáenz Moncaleano, Valeri AndreaJiménez Alzate, María del PilarBernal Giraldo, Adriana Jimenavirtual::18413-1Facultad de Ciencias::Grupo de Investigación Celular y Molecular de Microorganismos Patógenos (Cemop)2024-06-27T18:25:09Z2027-06-272024-06-052024-06-27https://hdl.handle.net/1992/74402instname:Universidad de los Andesreponame:Repositorio Institucional Sénecarepourl:https://repositorio.uniandes.edu.co/The primary objective of this doctoral thesis was to determine the presence of Fusarium and Neocosmospora in humans, animals, and plants through a One Health approach. To achieve this, we conducted phenotypic and molecular studies on samples obtained from various environments and human strains in Colombia to identify Fusarium or Neocosmospora. Our research revealed that Neocosmospora keratoplastica and Neocosmospora falciformis are prevalent in samples collected from humans, animals, and the environment (soil and sand). Notably, we describe Sea Turtle Egg Fusariosis (STEF) in sea turtles in Colombia for the first time. Furthermore, to find differences in how Fusarium/Neocosmospora interacts with hosts, we employed a Galleria mellonella animal model. We inoculated the larvae with clinical, animal, and environmental samples to carry out this experiment. We observed similar effects on mortality when the larvae were exposed to 1.5x106 UCF / ml of inoculum and incubated in a maintained incubation at 25 ° C. Also, it was observed that human, animal, and environmental samples can induce mortality in larvae at 37°C. Moreover, we determined the in vitro susceptibility profile of 52 isolates towards antifungal and fungicides. Our findings confirmed high Minimum Inhibitory Concentrations (MICs) to itraconazole, posaconazole, propiconazole, tebuconazole, and difenoconazole. However, amphotericin B and voriconazole showed susceptibility in most of the isolates. Subsequently, we aimed to investigate the antifungal effectiveness of molecules involved in Protein Kinase signaling pathways against Fusarium/Neocosmospora clinical isolates (n=12). To do this, we performed an in vitro test using four different inhibitors: the Pkc1 inhibitor (NPC15437), the p38 MAPK inhibitor (SKF 86002), the human Hsp90-Cdc37 inhibitor (Celastrol), and the antiparasitic drug Miltefosine. Our results indicate that the PKC1 inhibitor (NPC15437) and Miltefosine have promising antifungal activity. Finally, we address the challenges of diagnosing fungal keratitis in clinical and microbiologic settings. This was achieved through a survey of healthcare workers and collaboration with ophthalmologists, clinical microbiologists, and biodesigners to perform the design drafts and initial sketches of a medical device for corneal scraping.El objetivo principal de esta tesis doctoral fue determinar la presencia de Fusarium y Neocosmospora en humanos, animales y plantas utilizando un enfoque de Una Salud (One Health). Realizamos estudios fenotípicos y moleculares en muestras obtenidas de diversos ambientes y cepas humanas en Colombia, con el propósito de identificar Fusarium o Neocosmospora. Nuestra investigación reveló que Neocosmospora keratoplastica y Neocosmospora falciformis son especies prevalentes en muestras recolectadas de humanos, animales y el medio ambiente (suelo y arena). Cabe destacar que describimos por primera vez la fusariosis del huevo de tortuga marina (STEF) en tortugas marinas en Colombia. Además, para encontrar diferencias en cómo Fusarium/Neocosmospora interactúa con los huéspedes, empleamos un modelo animal de Galleria mellonella. Para realizar este experimento, inoculamos las larvas con muestras clínicas, animales y ambientales. Observamos efectos similares sobre la mortalidad cuando las larvas fueron expuestas a 1,5x106 UCF/ml de inóculo y se incubaron a 25°C. Además, se observó que muestras humanas, animales y ambientales pueden inducir mortalidad en larvas a 37°C. Además, determinamos el perfil de susceptibilidad in vitro de un total de 52 aislados, a antifúngicos y fungicidas. Nuestros hallazgos confirmaron concentraciones inhibidoras mínimas (CIM) elevadas para itraconazol, posaconazol, propiconazol, tebuconazol y difenoconazol. Sin embargo, la anfotericina B y el voriconazol mostraron susceptibilidad en la mayoría de los aislados. Posteriormente, nuestro objetivo fue investigar la eficacia antifúngica de las moléculas implicadas en las vías de señalización de la proteína quinasa contra aislados clínicos de Fusarium/Neocosmospora (n=12). Para ello, realizamos una prueba in vitro utilizando cuatro inhibidores diferentes, el inhibidor de Pkc1 (NPC15437), el inhibidor de p38 MAPK (SKF 86002), el inhibidor humano de Hsp90-Cdc37 (Celastrol) y el fármaco antiparasitario miltefosina. Nuestros resultados indican que el inhibidor de PKC1 (NPC15437) y la miltefosina tienen una actividad antifúngica prometedora. Finalmente, abordamos los desafíos del diagnóstico de queratitis fúngica en entornos clínicos y microbiológicos. Esto se logró mediante una encuesta realizada entre trabajadores de la salud. Así mismo, en colaboración con oftalmólogos, microbiólogos clínicos y biodiseñadores realizamos el diseño y bocetos iniciales de un dispositivo médico para el raspado de corneal.Proyecto semilla: INV-2020-97-1994, Interacción huésped- patógeno en aislamientos clínicos de Fusarium spp 3 de agosto de 2020 - 3 de agosto de 2021 Proyecto semilla: Resistencia a antifúngicos/fungicidas en Fusarium y Neocosmospora un acercamiento desde la iniciativa One Health (Una Salud). 1 de julio de 2023 - 1 de diciembre de 2023 Proyecto semilla: INV-2022-150-2583, Resistencia a antifúngicos/fungicidas en Fusarium y Neocosmospora un acercamiento desde la expresión de genes asociados a resistencia. 24 de enero de 2023 - 20 de enero de 2024DoctoradoFusaroidesInteracción hospedero-patógenoResistencia antimicrobiana236 páginasapplication/pdfengUniversidad de los AndesDoctorado en Ciencias - BiologíaFacultad de CienciasDepartamento de Ciencias BiológicasAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/embargoedAccesshttp://purl.org/coar/access_right/c_f1cfPathogenicity and resistance to antifungals-fungicides in Fusarium and Neocosmospora A One health approachEstudio de la patogenicidad y resistencia a antifúngicos /fungicidas en Fusarium y Neocosmospora: Una aproximación desde la iniciativa One HealthTrabajo de grado - Doctoradoinfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_db06Texthttps://purl.org/redcol/resource_type/TDFusariumNeocosmosporaOne healthSea turtle Egg FusariosisAntifungalFungicideBiología201122492Publicationhttps://scholar.google.es/citations?user=vQ9yFZoAAAAJhttps://scholar.google.es/citations?user=vQ9yFZoAAAAJvirtual::18413-10000-0003-3057-1966virtual::18411-10000-0002-3557-697Xvirtual::18413-10000-0002-3557-697Xhttps://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0000178225virtual::18411-1https://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0000622354virtual::18413-1https://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=00006223547ec7a7b4-b510-4816-b236-023aaa0754f0virtual::18411-17ec7a7b4-b510-4816-b236-023aaa0754f0virtual::18411-14e93f81c-d517-4226-80b7-2c5d693a24f4virtual::18413-14e93f81c-d517-4226-80b7-2c5d693a24f44e93f81c-d517-4226-80b7-2c5d693a24f4virtual::18413-1ORIGINALPathogenicity and resistance to antifungals-fungicides in Fusarium and Neocosmospora A One health approach.pdfPathogenicity and resistance to antifungals-fungicides in Fusarium and Neocosmospora A One health approach.pdfAlgunos capítulos de la tesis doctoral aun no están publicados. 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