{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T10:53:41Z","timestamp":1763376821889,"version":"3.45.0"},"reference-count":107,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["2024\/001"],"award-info":[{"award-number":["2024\/001"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Trypanosoma cruzi, the etiological agent of Chagas disease, exhibits remarkable developmental plasticity that enables its survival across distinct environments within the insect vector and mammalian host. This review focuses on two critical differentiation processes\u2014metacyclogenesis and epimastigogenesis\u2014emphasising their environmental triggers, metabolic regulation, and roles in parasite transmission and life cycle progression. Metacyclogenesis, occurring in the hindgut of triatomine vectors, transforms replicative epimastigotes into infective metacyclic trypomastigotes and is tightly controlled by factors such as nutrient starvation, pH, and temperature. In contrast, epimastigogenesis allows trypomastigotes to revert to epimastigote forms, primarily in the vector midgut, as part of the parasite\u2019s adaptation to vector colonisation. We compare these processes through the lens of stress-induced signalling and proteomic reprogramming, highlighting their metabolic divergence and ecological significance. Emerging evidence also suggests that extracellular vesicles (EVs) released by different parasite forms may actively modulate these transitions, supporting parasite communication and immune evasion strategies. A better understanding of these transitions provides novel insight into parasite adaptation and reveals potential molecular targets for disrupting the life cycle of T. cruzi.<\/jats:p>","DOI":"10.3390\/pathogens14111149","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T10:56:47Z","timestamp":1762945007000},"page":"1149","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Regulation and Roles of Metacyclogenesis and Epimastigogenesis in the Life Cycle of Trypanosoma cruzi"],"prefix":"10.3390","volume":"14","author":[{"given":"Abel","family":"Sana","sequence":"first","affiliation":[{"name":"EVAHPI-Extracellular Vesicles and Host-Parasite Interactions Research Group, Carlos Chagas Institute (Fiocruz-PR), Curitiba 81350-010, PR, Brazil"},{"name":"Graduate Program in Cell and Molecular Biology, Federal University of Paran\u00e1, Curitiba 81531-970, PR, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Izadora","family":"Rossi","sequence":"additional","affiliation":[{"name":"EVAHPI-Extracellular Vesicles and Host-Parasite Interactions Research Group, Carlos Chagas Institute (Fiocruz-PR), Curitiba 81350-010, PR, Brazil"},{"name":"Department of Immunology, Parasitology and General Pathology, State University of Londrina, Londrina 86057-970, PR, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel","family":"Ramirez","sequence":"additional","affiliation":[{"name":"EVAHPI-Extracellular Vesicles and Host-Parasite Interactions Research Group, Carlos Chagas Institute (Fiocruz-PR), Curitiba 81350-010, PR, Brazil"},{"name":"Graduate Program in Cell and Molecular Biology, Federal University of Paran\u00e1, Curitiba 81531-970, PR, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/S0020-7519(01)00153-9","article-title":"The life cycle of Trypanosoma cruzi revisited","volume":"31","author":"Tyler","year":"2001","journal-title":"Int. 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