{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T05:53:35Z","timestamp":1784872415226,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013784","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000}}],"reference-count":101,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R00AI137322"],"award-info":[{"award-number":["R00AI137322"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI182544"],"award-info":[{"award-number":["R21AI182544"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI178573"],"award-info":[{"award-number":["R21AI178573"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["23IPA1054779"],"award-info":[{"award-number":["23IPA1054779"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI148551"],"award-info":[{"award-number":["R01AI148551"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI166633"],"award-info":[{"award-number":["R21AI166633"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Cyclic AMP (cAMP) signaling is crucial for environmental sensing and response to stress conditions in trypanosomatids. However, the mechanisms driving the specificity of cAMP signals remain poorly understood in these protozoan parasites. We recently identified two putative cAMP microdomains in\n                    <jats:italic>Trypanosoma cruzi<\/jats:italic>\n                    , the causative agent of Chagas disease. Here, considering the localization of three phosphodiesterases, PDEC at the contractile vacuole complex (CVC), and PDEB1 and PDEB2 along the flagellum, we modulated their expression to functionally characterize the flagellar tip (FT) and the CVC as individual PDE-defined cAMP signaling compartments, named FT-cAMP and CVC-cAMP, respectively. We generated PDE knockout and overexpression cell lines to selectively alter cAMP signals generated in each compartment. Our results indicate that FT-cAMP mediates cell adhesion, metacyclogenesis, host cell invasion, and intracellular replication, while CVC-cAMP is important for osmoregulation and epimastigote proliferation. In addition, ablation of flagellar PDEB1 and PDEB2 enhanced the parasite\u2019s ability to colonize the hindgut of the triatomine vector, whereas PDEC-KO parasites were impaired in their establishment in the insect\u2019s hindgut. The observed phenotypes were PDE-specific, demonstrating functional segregation between the two compartments. Our data provide robust evidence on the presence of compartmentalized cAMP signals in\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    , linking the role of PDE-defined cAMP pools to specific cellular responses during the parasite\u2019s life cycle.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013784","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T17:42:18Z","timestamp":1782754938000},"page":"e1013784","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cyclic AMP compartmentalization drives signal specificity to control vector colonization and mammalian host infection by American trypanosomes"],"prefix":"10.1371","volume":"22","author":[{"given":"Milad","family":"Ahmed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Carlson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asima","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syeda Farjana","family":"Hoque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua B.","family":"Benoit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"Chiurillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2178-381X","authenticated-orcid":true,"given":"Noelia","family":"Lander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"issue":"1","key":"ppat.1013784.ref001","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/s41589-023-01381-8","article-title":"Cardiac contraction and relaxation are regulated by distinct subcellular cAMP pools","volume":"20","author":"T-Y Lin","year":"2024","journal-title":"Nat Chem Biol"},{"key":"ppat.1013784.ref002","first-page":"161","article-title":"Global and local missions of cAMP signaling in neural plasticity, learning, and memory","volume":"6","author":"D Lee","year":"2015","journal-title":"Front 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