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However, the effect of BLOC1S1 on\n                    <jats:italic>Brucella<\/jats:italic>\n                    autophagy has not yet been studied. This study investigates the interplay between\n                    <jats:italic>Brucella<\/jats:italic>\n                    lipopolysaccharide (LPS) and BLOC1S1 in modulating autophagy within goat spermatogonial stem cells (mGSCs\u2010I\u2010SB). Using LPS from\n                    <jats:italic>B. melitensis<\/jats:italic>\n                    16M, its capacity is demonstrated to induce AMPK\u2010dependent autophagy, contrasting with\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    LPS, which shows no significant effect. Mechanistically,\n                    <jats:italic>B. melitensis<\/jats:italic>\n                    16M LPS activates AMPK signaling, elevates LC3B\u2010II\/LC3B\u2010I ratios, and upregulates lysosomal and pro\u2010inflammatory genes. BLOC1S1 overexpression attenuates autophagy, reducing autolysosome formation (TEM) and LC3B\u2010II\/I ratio. RNA sequencing and proteomic analyses reveal BLOC1S1\u2010mediated transcriptional reprogramming of lysosomal pathways and mitochondrial metabolism. Co\u2010immunoprecipitation and subcellular localization studies reveal that TDP\u201043 is a key interacting partner and that BLOC1S1 sequesters TDP\u201043 in the cytoplasm, inhibiting its nuclear translocation\u2010dependent\n                    <jats:italic>ATG7<\/jats:italic>\n                    mRNA stability and enhancing autophagy. These findings delineate a dual regulatory mechanism:\n                    <jats:italic>B. melitensis<\/jats:italic>\n                    16M LPS\u2010driven, AMPK\u2010dependent autophagy induction, and BLOC1S1\u2010mediated autophagic suppression through spatial control of TDP\u201043. These results advance understanding of host\u2010pathogen interactions in brucellosis and identify BLOC1S1 as a potential therapeutic target for bacterial persistence and TDP\u201043\u2010related pathologies.\n                  <\/jats:p>","DOI":"10.1002\/advs.202505635","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T03:54:01Z","timestamp":1757649241000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["BLOC1S1 Attenuates\n                    <i>B. Melitensis<\/i>\n                    16M LPS\u2010Triggered Autophagy by Spatial Confinement of TDP\u201043"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6446-2339","authenticated-orcid":false,"given":"Shicheng","family":"Wan","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine Shaanxi Centre of Stem Cells Engineering &amp; Technology Northwest A&amp;F University  Yangling Shaanxi 712100 China"},{"name":"Guangzhou Eighth People's Hospital Guangzhou Medical University  Guangzhou 510440 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Han","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Shaanxi Centre of Stem Cells Engineering &amp; Technology Northwest A&amp;F University  Yangling Shaanxi 712100 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengfei","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Shaanxi Centre of Stem Cells Engineering &amp; Technology Northwest A&amp;F University  Yangling Shaanxi 712100 China"},{"name":"College of Veterinary Medicine Xinjiang Agricultural University  Urumqi 830000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbo","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Shaanxi Centre of Stem Cells Engineering &amp; Technology Northwest A&amp;F University  Yangling Shaanxi 712100 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangde","family":"Xie","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Shaanxi Centre of Stem Cells Engineering &amp; Technology Northwest A&amp;F University  Yangling Shaanxi 712100 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Luo","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Shaanxi Centre of Stem Cells Engineering &amp; Technology Northwest A&amp;F University  Yangling Shaanxi 712100 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenping","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Shaanxi Centre of Stem Cells Engineering &amp; Technology Northwest A&amp;F University  Yangling Shaanxi 712100 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congliang","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Shaanxi Centre of Stem Cells Engineering &amp; Technology Northwest A&amp;F University  Yangling Shaanxi 712100 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghui","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Shaanxi Centre of Stem Cells Engineering &amp; Technology Northwest A&amp;F University  Yangling Shaanxi 712100 China"},{"name":"Laboratory of Animal Disease Model College of Veterinary Medicine Sichuan Agricultural University  Chengdu 611130 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Han","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Xinjiang Agricultural University  Urumqi 830000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Shaanxi Provincial Engineering and Technology Research Center of Cashmere Goats Life Science Research Center Yulin University  Yulin 719000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haisheng","family":"Yu","sequence":"additional","affiliation":[{"name":"Guangzhou Eighth People's Hospital Guangzhou Medical University  Guangzhou 510440 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Shaanxi Centre of Stem Cells Engineering &amp; 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