{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:41:26Z","timestamp":1785426086005,"version":"3.56.0"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Xinjiang Tianshan Project","award":["2022TSYCLJ0032"],"award-info":[{"award-number":["2022TSYCLJ0032"]}]},{"name":"Key program of Xinjiang Natural Science Foundation","award":["2022D01D59"],"award-info":[{"award-number":["2022D01D59"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82060371, 81260252"],"award-info":[{"award-number":["82060371, 81260252"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Cystic echinococcosis (CE), a zoonosis caused by the larval stage of the tapeworm\n                      <jats:italic toggle=\"yes\">Echinococcus granulosus sensu lato<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">E. granulosus s.l<\/jats:italic>\n                      .), remains a global health burden. Despite the conserved role of the transforming growth factor beta (TGF\u03b2)\/Smad signaling in cellular regulation across species, the molecular mechanisms of TGF\u03b2\/bone morphogenetic proteins (BMP) receptors in\n                      <jats:italic toggle=\"yes\">E. granulosus sensu stricto<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">E. granulosus s.s<\/jats:italic>\n                      .) are poorly understood. The TGF\u03b2\/BMP receptors of\n                      <jats:italic toggle=\"yes\">E. granulosus s.s<\/jats:italic>\n                      . were cloned and molecularly characterized. The positive binding interaction between receptors and their ligands was identified using the yeast two-hybrid system. To investigate the role of TGF\u03b2\/BMP signaling in\n                      <jats:italic toggle=\"yes\">E. granulosus s.s<\/jats:italic>\n                      . development and survival, LDN193189 was employed in both the\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      co-culture system and subsequent\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      bioassays to investigate its pharmacological effects. Both receptors,\n                      <jats:italic toggle=\"yes\">E. granulosus<\/jats:italic>\n                      type I receptor (EgTR1) and type II receptor (EgTR2), were characterized in\n                      <jats:italic toggle=\"yes\">E. granulosus s.s<\/jats:italic>\n                      . and expressed during the larval stages, with\n                      <jats:italic toggle=\"yes\">egtr2<\/jats:italic>\n                      showing peak transcriptional levels in activated protoscoleces (PSCs), 40-fold higher than those in cysts.\n                      <jats:italic toggle=\"yes\">In situ<\/jats:italic>\n                      immunofluorescence analysis demonstrated a predominant localization of EgTR1 and EgTR2 within the tegument, suckers, and hooks of PSCs, as well as in the germinal layer of larval cysts. Yeast two-hybrid analysis revealed that EgTR2 interacted with EgTR1 and HsBMP2, but not with HsTGF\u03b2. LDN193189 treatment significantly suppressed the viability of PSCs.\n                      <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                      bioassays in mice demonstrated a notable reduction in the weight of cysts in the LDN193189-treated group compared with the dimethyl sulfoxide-treated group. Our results suggest that EgTR1 and EgTR2 regulate\n                      <jats:italic toggle=\"yes\">E. granulosus s.s<\/jats:italic>\n                      . development\n                      <jats:italic toggle=\"yes\">,<\/jats:italic>\n                      identifying TGF\u03b2\/BMP signaling as a therapeutic target for CE.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Cystic echinococcosis (CE), a neglected zoonosis caused by\n                        <jats:italic toggle=\"yes\">E. granulosus s.l<\/jats:italic>\n                        ., inflicts severe morbidity and economic losses globally. While transforming growth factor beta\/bone morphogenetic proteins (TGF\u03b2\/BMP) signaling regulates cellular processes across species, its functional role in\n                        <jats:italic toggle=\"yes\">E. granulosus s.s.<\/jats:italic>\n                        remains unexplored. Here, we elucidate the molecular basis of TGF\u03b2\/BMP receptor signaling in\n                        <jats:italic toggle=\"yes\">E. granulosus s.s.<\/jats:italic>\n                        , revealing that\n                        <jats:italic toggle=\"yes\">E. granulosus<\/jats:italic>\n                        type I receptor (EgTR1) and type II receptor (EgTR2) orchestrate larval development through species-specific ligand interactions. Our findings demonstrate that EgTR2 interacts with Human BMP2 (HsBMP2), establishing a unique parasitic adaptation mechanism. Pharmacological inhibition using LDN193189 caused the suppression of parasite viability\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        and reduced cyst weight\n                        <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                        , validating these receptors as druggable targets. This study provides the evidence linking TGF\u03b2\/BMP receptor dynamics to parasitic survival strategies, while identifying a clinically accessible therapeutic avenue for CE. The discovery bridges a critical gap in parasitic helminth biology and advances precision medicine approaches for combating this neglected tropical disease.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01318-25","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T17:39:25Z","timestamp":1764178765000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Functional characterization of TGF\u03b2\/BMP receptors in\n                    <i>Echinococcus granulosus sensu stricto<\/i>\n                    : implications for parasite survival and therapeutic 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