{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T18:26:39Z","timestamp":1773685599646,"version":"3.50.1"},"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The National Key Research and Development Program of China","award":["2023YFE0107300"],"award-info":[{"award-number":["2023YFE0107300"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NSFC32302960"],"award-info":[{"award-number":["NSFC32302960"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32373032"],"award-info":[{"award-number":["32373032"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007847","name":"Natural Science Foundation of Jilin Province","doi-asserted-by":"publisher","award":["20220508052RC"],"award-info":[{"award-number":["20220508052RC"]}],"id":[{"id":"10.13039\/100007847","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Trichinella spiralis<\/jats:italic>\n                    (\n                    <jats:italic>T. spiralis<\/jats:italic>\n                    ), a zoonotic nematode that causes severe myositis and systemic morbidity, sustains chronic muscle parasitism through evolutionary adaptations; however, this globally prevalent disease lacks targeted therapies to disrupt chronic infection. Although the heme transport protein HRG-1 has been characterized as an intervention target in free-living species (e.g.,\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    ) and hematophagous parasites (e.g.,\n                    <jats:italic>Haemonchus contortus<\/jats:italic>\n                    ), the molecular machinery governing heme acquisition in the nonhematophagous parasite\n                    <jats:italic>T. spiralis<\/jats:italic>\n                    remains uncharacterized, and no drugs targeting HRG-1 have been reported until now. Herein, we demonstrate that\n                    <jats:italic>T. spiralis<\/jats:italic>\n                    , a parasite that lacks the ability to synthesize heme autonomously, has evolved a sophisticated mechanism to scavenge and utilize heme from its host. By employing an aspartic protease to degrade host hemoglobin and myoglobin in the parasitic niche,\n                    <jats:italic>T. spiralis<\/jats:italic>\n                    is able to liberate heme for its own growth and survival. The structurally and functionally conserved\n                    <jats:italic>Ts<\/jats:italic>\n                    -HRG-1 protein plays a key role in transporting heme to the entire worm, particularly to functional organs, such as the cuticle and stichosome. More importantly, we discovered that the interaction between\n                    <jats:italic>Ts<\/jats:italic>\n                    -HRG-1 and\n                    <jats:italic>Ts<\/jats:italic>\n                    -ATP6V0C results in the formation of a functional complex that is essential for the parasite\u2019s heme acquisition. The intervention effect achieved by\n                    <jats:italic>Ts<\/jats:italic>\n                    -ATP6V0C RNAi or inhibiting the activity of\n                    <jats:italic>Ts<\/jats:italic>\n                    -ATP6V0C with bafilomycin A1 (BafA1) was consistent with\n                    <jats:italic>Ts<\/jats:italic>\n                    -HRG-1 RNAi, resulting in impaired heme uptake, developmental arrest and a reduced larval burden in mouse hosts. These findings enhance our understanding of the parasite\u2019s heme acquisition mechanism and identify the development of drugs that target proteins that interact with HRG-1 as a new direction in anthelminthic drug research.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014042","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T17:31:51Z","timestamp":1773682311000},"page":"e1014042","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bafilomycin A1 is a promising therapeutic agent against T. spiralis infection by inhibiting the heme-transporting ATP6V0C\/HRG-1 complex"],"prefix":"10.1371","volume":"22","author":[{"given":"Yushu","family":"He","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoying","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingbo","family":"Lv","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Vallee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascal","family":"Boireau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8262-0876","authenticated-orcid":true,"given":"Xiaolei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"ppat.1014042.ref001","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.fm.2016.12.012","article-title":"Meat 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