True cyst formation underlies persistence and drug tolerance in Tritrichomonas foetus

Autores
Iriarte, Lucrecia Soledad; Alonso, Andrés Mariano; Villarreal, Natalia Marina; Martinez, Cristian Israel; Prandi, María Sol; Barros, Luiz D.; Ferrante, Marcos; de Miguel, Natalia; Cóceres, Verónica Mabel
Año de publicación
2026
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Tritrichomonas foetus, a protozoan parasite responsible for bovine and feline trichomonosis, has traditionally been considered to form only pseudocysts. Here, we demonstrate that T. foetus produces true cysts characterized by a chitin-like, fibrillar wall, cytoskeletal reorganization, and resistance to detergent treatment. Using scanning and transmission electron microscopy, sarkosyl resistance assays, lectin and chitin-binding staining, and monosaccharide composition analysis, we identify a polysaccharide-rich cyst wall enriched in N-acetylated hexosamines. Cystogenesis is induced by environmental stresses, including nutrient deprivation, alkaline pH mimicking the bovine preputial environment, and metronidazole exposure. Flow cytometry analyses reveal increased DNA content and multinucleation in cysts, consistent with endoreplication. Encysted parasites remain viable and revert to proliferative trophozoites upon restoration of favorable conditions. Pharmacological inhibition of cyst wall biosynthesis enhances metronidazole susceptibility, supporting a functional role for cyst formation in drug tolerance. Transcriptomic profiling identifies pathways associated with carbohydrate metabolism, Myb-like transcription factors, and calcium/calmodulin-dependent kinases during encystation. Together, our findings establish true cyst formation in T. foetus and define a previously unrecognized survival state linked to environmental persistence and reduced drug susceptibility.
Fil: Iriarte, Lucrecia Soledad. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
Fil: Alonso, Andrés Mariano. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
Fil: Villarreal, Natalia Marina. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
Fil: Martinez, Cristian Israel. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
Fil: Prandi, María Sol. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
Fil: Barros, Luiz D.. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
Fil: Ferrante, Marcos. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
Fil: de Miguel, Natalia. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
Fil: Cóceres, Verónica Mabel. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
Materia
cyst
parasite
drug resistance
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/290028
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/290028
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling True cyst formation underlies persistence and drug tolerance in Tritrichomonas foetusIriarte, Lucrecia SoledadAlonso, Andrés MarianoVillarreal, Natalia MarinaMartinez, Cristian IsraelPrandi, María SolBarros, Luiz D.Ferrante, Marcosde Miguel, NataliaCóceres, Verónica Mabelcystparasitedrug resistancehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Tritrichomonas foetus, a protozoan parasite responsible for bovine and feline trichomonosis, has traditionally been considered to form only pseudocysts. Here, we demonstrate that T. foetus produces true cysts characterized by a chitin-like, fibrillar wall, cytoskeletal reorganization, and resistance to detergent treatment. Using scanning and transmission electron microscopy, sarkosyl resistance assays, lectin and chitin-binding staining, and monosaccharide composition analysis, we identify a polysaccharide-rich cyst wall enriched in N-acetylated hexosamines. Cystogenesis is induced by environmental stresses, including nutrient deprivation, alkaline pH mimicking the bovine preputial environment, and metronidazole exposure. Flow cytometry analyses reveal increased DNA content and multinucleation in cysts, consistent with endoreplication. Encysted parasites remain viable and revert to proliferative trophozoites upon restoration of favorable conditions. Pharmacological inhibition of cyst wall biosynthesis enhances metronidazole susceptibility, supporting a functional role for cyst formation in drug tolerance. Transcriptomic profiling identifies pathways associated with carbohydrate metabolism, Myb-like transcription factors, and calcium/calmodulin-dependent kinases during encystation. Together, our findings establish true cyst formation in T. foetus and define a previously unrecognized survival state linked to environmental persistence and reduced drug susceptibility.Fil: Iriarte, Lucrecia Soledad. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; ArgentinaFil: Alonso, Andrés Mariano. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; ArgentinaFil: Villarreal, Natalia Marina. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; ArgentinaFil: Martinez, Cristian Israel. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; ArgentinaFil: Prandi, María Sol. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; ArgentinaFil: Barros, Luiz D.. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; ArgentinaFil: Ferrante, Marcos. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; ArgentinaFil: de Miguel, Natalia. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; ArgentinaFil: Cóceres, Verónica Mabel. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; ArgentinaNature2026-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/290028Iriarte, Lucrecia Soledad; Alonso, Andrés Mariano; Villarreal, Natalia Marina; Martinez, Cristian Israel; Prandi, María Sol; et al.; True cyst formation underlies persistence and drug tolerance in Tritrichomonas foetus; Nature; Nature Communications; 4-2026; 1-332041-1723CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41467-026-71827-9info:eu-repo/semantics/altIdentifier/doi/10.1038/s41467-026-71827-9info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-08-25T14:45:32Zoai:ri.conicet.gov.ar:11336/290028instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982026-08-25 14:45:32.726CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv True cyst formation underlies persistence and drug tolerance in Tritrichomonas foetus
title True cyst formation underlies persistence and drug tolerance in Tritrichomonas foetus
spellingShingle True cyst formation underlies persistence and drug tolerance in Tritrichomonas foetus
Iriarte, Lucrecia Soledad
cyst
parasite
drug resistance
title_short True cyst formation underlies persistence and drug tolerance in Tritrichomonas foetus
title_full True cyst formation underlies persistence and drug tolerance in Tritrichomonas foetus
title_fullStr True cyst formation underlies persistence and drug tolerance in Tritrichomonas foetus
title_full_unstemmed True cyst formation underlies persistence and drug tolerance in Tritrichomonas foetus
title_sort True cyst formation underlies persistence and drug tolerance in Tritrichomonas foetus
dc.creator.none.fl_str_mv Iriarte, Lucrecia Soledad
Alonso, Andrés Mariano
Villarreal, Natalia Marina
Martinez, Cristian Israel
Prandi, María Sol
Barros, Luiz D.
Ferrante, Marcos
de Miguel, Natalia
Cóceres, Verónica Mabel
author Iriarte, Lucrecia Soledad
author_facet Iriarte, Lucrecia Soledad
Alonso, Andrés Mariano
Villarreal, Natalia Marina
Martinez, Cristian Israel
Prandi, María Sol
Barros, Luiz D.
Ferrante, Marcos
de Miguel, Natalia
Cóceres, Verónica Mabel
author_role author
author2 Alonso, Andrés Mariano
Villarreal, Natalia Marina
Martinez, Cristian Israel
Prandi, María Sol
Barros, Luiz D.
Ferrante, Marcos
de Miguel, Natalia
Cóceres, Verónica Mabel
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv cyst
parasite
drug resistance
topic cyst
parasite
drug resistance
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Tritrichomonas foetus, a protozoan parasite responsible for bovine and feline trichomonosis, has traditionally been considered to form only pseudocysts. Here, we demonstrate that T. foetus produces true cysts characterized by a chitin-like, fibrillar wall, cytoskeletal reorganization, and resistance to detergent treatment. Using scanning and transmission electron microscopy, sarkosyl resistance assays, lectin and chitin-binding staining, and monosaccharide composition analysis, we identify a polysaccharide-rich cyst wall enriched in N-acetylated hexosamines. Cystogenesis is induced by environmental stresses, including nutrient deprivation, alkaline pH mimicking the bovine preputial environment, and metronidazole exposure. Flow cytometry analyses reveal increased DNA content and multinucleation in cysts, consistent with endoreplication. Encysted parasites remain viable and revert to proliferative trophozoites upon restoration of favorable conditions. Pharmacological inhibition of cyst wall biosynthesis enhances metronidazole susceptibility, supporting a functional role for cyst formation in drug tolerance. Transcriptomic profiling identifies pathways associated with carbohydrate metabolism, Myb-like transcription factors, and calcium/calmodulin-dependent kinases during encystation. Together, our findings establish true cyst formation in T. foetus and define a previously unrecognized survival state linked to environmental persistence and reduced drug susceptibility.
Fil: Iriarte, Lucrecia Soledad. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
Fil: Alonso, Andrés Mariano. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
Fil: Villarreal, Natalia Marina. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
Fil: Martinez, Cristian Israel. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
Fil: Prandi, María Sol. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
Fil: Barros, Luiz D.. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
Fil: Ferrante, Marcos. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
Fil: de Miguel, Natalia. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
Fil: Cóceres, Verónica Mabel. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
description Tritrichomonas foetus, a protozoan parasite responsible for bovine and feline trichomonosis, has traditionally been considered to form only pseudocysts. Here, we demonstrate that T. foetus produces true cysts characterized by a chitin-like, fibrillar wall, cytoskeletal reorganization, and resistance to detergent treatment. Using scanning and transmission electron microscopy, sarkosyl resistance assays, lectin and chitin-binding staining, and monosaccharide composition analysis, we identify a polysaccharide-rich cyst wall enriched in N-acetylated hexosamines. Cystogenesis is induced by environmental stresses, including nutrient deprivation, alkaline pH mimicking the bovine preputial environment, and metronidazole exposure. Flow cytometry analyses reveal increased DNA content and multinucleation in cysts, consistent with endoreplication. Encysted parasites remain viable and revert to proliferative trophozoites upon restoration of favorable conditions. Pharmacological inhibition of cyst wall biosynthesis enhances metronidazole susceptibility, supporting a functional role for cyst formation in drug tolerance. Transcriptomic profiling identifies pathways associated with carbohydrate metabolism, Myb-like transcription factors, and calcium/calmodulin-dependent kinases during encystation. Together, our findings establish true cyst formation in T. foetus and define a previously unrecognized survival state linked to environmental persistence and reduced drug susceptibility.
publishDate 2026
dc.date.none.fl_str_mv 2026-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/290028
Iriarte, Lucrecia Soledad; Alonso, Andrés Mariano; Villarreal, Natalia Marina; Martinez, Cristian Israel; Prandi, María Sol; et al.; True cyst formation underlies persistence and drug tolerance in Tritrichomonas foetus; Nature; Nature Communications; 4-2026; 1-33
2041-1723
CONICET Digital
CONICET
url http://hdl.handle.net/11336/290028
identifier_str_mv Iriarte, Lucrecia Soledad; Alonso, Andrés Mariano; Villarreal, Natalia Marina; Martinez, Cristian Israel; Prandi, María Sol; et al.; True cyst formation underlies persistence and drug tolerance in Tritrichomonas foetus; Nature; Nature Communications; 4-2026; 1-33
2041-1723
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41467-026-71827-9
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41467-026-71827-9
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature
publisher.none.fl_str_mv Nature
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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