{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T23:14:35Z","timestamp":1792710875578,"version":"4.5.0"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"52","license":[{"start":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T00:00:00Z","timestamp":1734566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"HHS | NIH | NIAID | Division of Intramural Research","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,12,24]]},"abstract":"<jats:p>\n                    Sandfly vectors transmit\n                    <jats:italic>Leishmania<\/jats:italic>\n                    through egestion of parasites into the host skin. The transmissible dose is shaped by\n                    <jats:italic>Leishmania<\/jats:italic>\n                    development in the sandfly gut, described as a sequential differentiation of promastigote morphotypes. Apart from isolated mammal-infective metacyclic promastigotes, little is known about the transcriptional programs and molecular markers for other stages coinhabiting the midgut in mature infections and cotransmitted by the sandfly bite. Here, we elucidate the single-cell transcriptomic complexity of\n                    <jats:italic>Leishmania major<\/jats:italic>\n                    colonizing its natural vector\n                    <jats:italic>Phlebotomus duboscqi<\/jats:italic>\n                    at early and late infection, providing markers for three transmissible stages. Contrary to prevailing models, our analyses indicate a nonlinear developmental progression, with bifurcation into either replicating early metacyclics or attached and detached haptomonads. We demonstrate that haptomonads constitute a key component of the transmitted inoculum and, along with nondividing late metacyclics, are infectious to and exacerbate the pathology in mice. Our single-cell analysis and validated markers will facilitate further studies on the\n                    <jats:italic>Leishmania<\/jats:italic>\n                    life cycle and its implications for vector-to-host transmission dynamics.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2406776121","type":"journal-article","created":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T13:40:01Z","timestamp":1734615601000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":33,"title":["Single-cell atlas of\n                    <i>Leishmania<\/i>\n                    development in sandflies reveals the heterogeneity of transmitted parasites and their role in infection"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8983-3487","authenticated-orcid":false,"given":"Carolina M. C.","family":"Catta-Preta","sequence":"first","affiliation":[{"name":"Intracellular Parasite Biology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH","place":["Bethesda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kashinath","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Intracellular Parasite Biology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH","place":["Bethesda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7557-3124","authenticated-orcid":false,"given":"David L.","family":"Sacks","sequence":"additional","affiliation":[{"name":"Intracellular Parasite Biology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH","place":["Bethesda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4894-1515","authenticated-orcid":false,"given":"Tiago R.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Intracellular Parasite Biology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH","place":["Bethesda"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,12,19]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182002001439"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2007.04.003"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-7519(03)00142-5"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.20.9944"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2008.01132.x"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-018-0125-7"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00029-17"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0008014"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-018-4772-0"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3560335"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2010.01507.x"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-020-07025-8"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-019-0323-8"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006130"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/1756-3305-5-276"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-51291-z"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.86325"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14766-3"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008042"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.73488"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42789-z"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06655-8"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-9-255"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200500853"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv656"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6701528"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0020-7519(89)90043-X"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1051\/parasite\/1988632134"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1051\/parasite\/1990651037"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02858-22"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009904"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010346"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007288"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2020.118694"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2006.06.027"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2012.01798.x"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.84552"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1986.35.926"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1017\/S003118200008183X"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0802331105"},{"key":"e_1_3_4_41_2","unstructured":"C. M. C. Catta-Preta T. R. Ferreira Single-cell RNA-sequencing of Leishmania major forms during Phlebotomus duboscqi infection. NCBI Sequence Read Archive (SRA). https:\/\/www.ncbi.nlm.nih.gov\/bioproject\/PRJNA1082770. Deposited 1 March 2024."},{"key":"e_1_3_4_42_2","doi-asserted-by":"crossref","unstructured":"C. M. C. Catta-Preta T. R. Ferreira scRNA-seq data for article: Single-cell atlas of Leishmania major development in the sandfly vector reveals the heterogeneity of transmitted promastigotes and their impact on infection. Zenodo. https:\/\/doi.org\/10.5281\/zenodo.10779511. 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