{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T09:52:56Z","timestamp":1787997176555,"version":"build-2784847793"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"State Key Research Development Program of China","award":["2022YFE0102200"],"award-info":[{"award-number":["2022YFE0102200"]}]},{"DOI":"10.13039\/100008349","name":"Boehringer Ingelheim International GmbH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002365","name":"China Agricultural University","doi-asserted-by":"publisher","award":["00109029"],"award-info":[{"award-number":["00109029"]}],"id":[{"id":"10.13039\/501100002365","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tuberculosis (TB) caused by the Mycobacterium tuberculosis complex (MTBC) is the leading cause of death from a single infectious agent worldwide. Current antibiotics fail against drug-resistant strains, highlighting the urgent need for novel therapies. Host-directed therapy (HDT), which enhances host immunity rather than targeting pathogens directly, offers a promising solution.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We use the in vitro cells infection assays and in vivo mouse infection model to identify the effects of a monovalent second mitochondria-derived activator of caspase (SMAC) mimetic named BI82 against mycobacterial infections.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We demonstrate that BI82 potently inhibits Mycobacterium bovis growth in macrophages, while exhibiting synergy with rifampicin. BI82 also significantly restricts M. tuberculosis growth in ex vivo whole-blood assays from both tuberculosis patients and healthy donors. BI82 degrades cellular inhibitor of apoptosis protein 1 (cIAP1), promoting infected cell apoptosis as evidenced by elevated cleaved caspase-3 and phosphorylated mixed lineage kinase domain-like levels. In a mouse model, oral BI82 treatment can reduce M. bovis burden in lungs and spleens, alleviate lung lesions, and increase CD3\u207a T cells with elevated CD4\/CD8 ratios.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings reveal that BI82 employs a unique apoptosis-dependent mechanism to exert broad-spectrum activity against mycobacterial infections, positioning it as a promising HDT candidate.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiag031","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T12:50:39Z","timestamp":1767963039000},"page":"777-786","source":"Crossref","is-referenced-by-count":1,"title":["A Monovalent SMAC Mimetic as a Potential Host-Directed Therapy for Tuberculosis"],"prefix":"10.1093","volume":"233","author":[{"given":"Jiahong","family":"Ji","sequence":"first","affiliation":[{"name":"State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyi","family":"Jiang","sequence":"additional","affiliation":[{"name":"National Clinical Laboratory on Tuberculosis, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing Chest Hospital, Capital Medical University , Beijing ,","place":["China"]},{"name":"Department of Clinical Laboratory, Beijing Chaoyang Hospital, Capital Medical University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlei","family":"Liao","sequence":"additional","affiliation":[{"name":"National Clinical Laboratory on Tuberculosis, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing Chest Hospital, Capital 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Beijing Chest Hospital, Capital Medical University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Mei","sequence":"additional","affiliation":[{"name":"Chinese Institutes for Medical Research, Beijing You\u2019an Hospital, Capital Medical University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"He","sequence":"additional","affiliation":[{"name":"Wisdom Lake Academy of Pharmacy, Xi\u2019an Jiaotong-Liverpool University , Suzhou ,","place":["China"]},{"name":"Research Beyond Borders, Boehringer Ingelheim , Shanghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Tan","sequence":"additional","affiliation":[{"name":"Chinese Institutes for Medical Research, Beijing You\u2019an Hospital, Capital Medical University , Beijing 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