Oryzalin but not Itraconazole disrupts CTP synthase localization in some Toxoplasma gondii tachyzoites
Toxoplasmosis is a worldwide prevalent infection caused by the Toxoplasma gondii parasite, that could lead to several diseases especially in new-borns and immunocompromised patients, therefore, discovery of novel drug targets has become a major concern. The pyrimidine pathway has been proposed as a...
- Autores:
-
Gutiérrez Melo, Nicolás
- Tipo de recurso:
- Trabajo de grado de pregrado
- Fecha de publicación:
- 2017
- Institución:
- Universidad de los Andes
- Repositorio:
- Séneca: repositorio Uniandes
- Idioma:
- eng
- OAI Identifier:
- oai:repositorio.uniandes.edu.co:1992/61471
- Acceso en línea:
- http://hdl.handle.net/1992/61471
- Palabra clave:
- Enzimas
Interacciones proteína-proteína
Parasitología
Toxoplasma gondii
- Rights
- openAccess
- License
- http://creativecommons.org/licenses/by-nc-sa/4.0/
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| dc.title.spa.fl_str_mv |
Oryzalin but not Itraconazole disrupts CTP synthase localization in some Toxoplasma gondii tachyzoites |
| title |
Oryzalin but not Itraconazole disrupts CTP synthase localization in some Toxoplasma gondii tachyzoites |
| spellingShingle |
Oryzalin but not Itraconazole disrupts CTP synthase localization in some Toxoplasma gondii tachyzoites Enzimas Interacciones proteína-proteína Parasitología Toxoplasma gondii |
| title_short |
Oryzalin but not Itraconazole disrupts CTP synthase localization in some Toxoplasma gondii tachyzoites |
| title_full |
Oryzalin but not Itraconazole disrupts CTP synthase localization in some Toxoplasma gondii tachyzoites |
| title_fullStr |
Oryzalin but not Itraconazole disrupts CTP synthase localization in some Toxoplasma gondii tachyzoites |
| title_full_unstemmed |
Oryzalin but not Itraconazole disrupts CTP synthase localization in some Toxoplasma gondii tachyzoites |
| title_sort |
Oryzalin but not Itraconazole disrupts CTP synthase localization in some Toxoplasma gondii tachyzoites |
| dc.creator.fl_str_mv |
Gutiérrez Melo, Nicolás |
| dc.contributor.advisor.none.fl_str_mv |
Zimmermann, Barbara Hanna |
| dc.contributor.author.none.fl_str_mv |
Gutiérrez Melo, Nicolás |
| dc.subject.keyword.spa.fl_str_mv |
Enzimas Interacciones proteína-proteína Parasitología Toxoplasma gondii |
| topic |
Enzimas Interacciones proteína-proteína Parasitología Toxoplasma gondii |
| description |
Toxoplasmosis is a worldwide prevalent infection caused by the Toxoplasma gondii parasite, that could lead to several diseases especially in new-borns and immunocompromised patients, therefore, discovery of novel drug targets has become a major concern. The pyrimidine pathway has been proposed as a possible drug target, since apicomplexan enzymes vary from those of humans. Previous studies have shown that inhibition of CTP synthase with the glutamine antagonist 6-diazo-5-oxo-L-norleucine (DON), disrupts tachyzoites' morphology and reduces significantly the infection progression. A similar phenomenon has been described with inhibitors such as oryzalin and itraconazole but the exact mechanism has not been clearly elucidated yet. Consequently, the aim of this study was to determine if CTP synthase is affected by the inhibition effect during treatment with oryzalin and itraconazole. T. gondii tachyzoites were cultured in HFF cells and treated with 2 uM Itraconazole, 0.5 and 2.5 uM oryzalin, or 30 uM DON, or with combinations of inhibitors. Infected host cells were fixed 28 hours post infection and CTP synthase localization was assessed using immunofluorescence. Parasites treated with itraconazole alone or in combination with DON did not display any significant differences in enzyme localization compared to those observed in control treatments. However, incubation with oryzalin appeared to affect CTP synthase distribution since protein aggregates tended to localize towards the sides of some of the tachyzoites. These results suggest that CTP synthase might be involved in parasite morphology but stronger evidence is needed. |
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2017 |
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2017 |
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2022-09-26T22:22:05Z |
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2022-09-26T22:22:05Z |
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Universidad de los Andes |
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Microbiología |
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Facultad de Ciencias |
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Departamento de Ciencias Biológicas |
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Al consultar y hacer uso de este recurso, está aceptando las condiciones de uso establecidas por los autores.http://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Zimmermann, Barbara Hanna81271423-588b-479b-a844-0d7443608a49500Gutiérrez Melo, Nicolás56425af1-2ff9-44a3-a208-702a35c15b185002022-09-26T22:22:05Z2022-09-26T22:22:05Z2017http://hdl.handle.net/1992/61471instname:Universidad de los Andesreponame:Repositorio Institucional Sénecarepourl:https://repositorio.uniandes.edu.co/795170-1001Toxoplasmosis is a worldwide prevalent infection caused by the Toxoplasma gondii parasite, that could lead to several diseases especially in new-borns and immunocompromised patients, therefore, discovery of novel drug targets has become a major concern. The pyrimidine pathway has been proposed as a possible drug target, since apicomplexan enzymes vary from those of humans. Previous studies have shown that inhibition of CTP synthase with the glutamine antagonist 6-diazo-5-oxo-L-norleucine (DON), disrupts tachyzoites' morphology and reduces significantly the infection progression. A similar phenomenon has been described with inhibitors such as oryzalin and itraconazole but the exact mechanism has not been clearly elucidated yet. Consequently, the aim of this study was to determine if CTP synthase is affected by the inhibition effect during treatment with oryzalin and itraconazole. T. gondii tachyzoites were cultured in HFF cells and treated with 2 uM Itraconazole, 0.5 and 2.5 uM oryzalin, or 30 uM DON, or with combinations of inhibitors. Infected host cells were fixed 28 hours post infection and CTP synthase localization was assessed using immunofluorescence. Parasites treated with itraconazole alone or in combination with DON did not display any significant differences in enzyme localization compared to those observed in control treatments. However, incubation with oryzalin appeared to affect CTP synthase distribution since protein aggregates tended to localize towards the sides of some of the tachyzoites. These results suggest that CTP synthase might be involved in parasite morphology but stronger evidence is needed.La toxoplasmosis es una infección prevalente en todo el mundo causada por el parásito Toxoplasma gondii y que puede conducir a varias enfermedades especialmente en recién nacidos y pacientes inmunocomprometidos, razón por la cual, el descubrimiento de nuevos blancos terapéuticos se ha convertido en una preocupación importante. La vía de síntesis de las pirimidinas se ha propuesto como un posible objetivo de fármaco, ya que las enzimas del filo apicomplexa difieren significativamente de las de los seres humanos. Estudios previos han demostrado que la inhibición de la CTP sintasa con el antagonista de la glutamina 6-diazo-5-oxo-L-norleucina (DON), altera la morfología de los taquizoítos y reduce radicalmente la progresión de la infección. Un fenómeno similar se ha descrito con inhibidores tales como oryzalin e itraconazol pero el mecanismo exacto de aún no se conoce con claridad. En consecuencia, el objetivo de este estudio fue determinar si la CTP sintasa se ve afectada por la inhibición durante el tratamiento con oryzalin e itraconazol. Los taquizoitos de T. gondii se cultivaron en células HFF y se trataron con itraconazol 2 uM, oryzalin 0,5 y 2,5 uM o DON 30 uM, o con combinaciones de inhibidores. Las células huésped infectadas se fijaron 28 horas post infección y la localización de CTP sintasa se evaluó utilizando inmunofluorescencia. Los parásitos tratados con itraconazol solo o en combinación con DON no mostraron diferencias significativas en la localización enzimática en comparación con los observados en el tratamiento control. Sin embargo, la incubación con oryzalin parece afectar la distribución de la CTP sintasa, ya que los agregados de proteínas tienden a desplazarse hacia los lados en algunos taquizoitos. Estos resultados sugieren que la CTP sintasa podría estar involucrada en la morfología del parásito, no obstante, mayor evidencia es necesaria para soportarlo.--Tomado del Formato de Documento de Grado.MicrobiólogoPregrado14 hojasapplication/pdfengUniversidad de los AndesMicrobiologíaFacultad de CienciasDepartamento de Ciencias BiológicasOryzalin but not Itraconazole disrupts CTP synthase localization in some Toxoplasma gondii tachyzoitesTrabajo de grado - Pregradoinfo:eu-repo/semantics/bachelorThesisinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_7a1fTexthttp://purl.org/redcol/resource_type/TPEnzimasInteracciones proteína-proteínaParasitologíaToxoplasma gondii201224433PublicationTEXT12954.pdf.txt12954.pdf.txtExtracted texttext/plain25785https://repositorio.uniandes.edu.co/bitstreams/f3e40c15-ade9-4db2-b2fe-0169578c1391/downloada3443dd6b32a2811cd9c5f17f0136345MD52THUMBNAIL12954.pdf.jpg12954.pdf.jpgIM Thumbnailimage/jpeg20488https://repositorio.uniandes.edu.co/bitstreams/f78891b4-70c3-487a-aee2-25187da52f52/download1d2216c5154934bcd1f3f7fec97d317aMD53ORIGINAL12954.pdfapplication/pdf344963https://repositorio.uniandes.edu.co/bitstreams/cbea6748-e6c8-4f98-8077-a21716caec7c/downloada9aead91c806bcfe5c05f5bf24dbf900MD511992/61471oai:repositorio.uniandes.edu.co:1992/614712023-10-10 15:46:24.604http://creativecommons.org/licenses/by-nc-sa/4.0/open.accesshttps://repositorio.uniandes.edu.coRepositorio institucional Sénecaadminrepositorio@uniandes.edu.co |