{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T23:34:20Z","timestamp":1768520060981,"version":"3.49.0"},"posted":{"date-parts":[[2024,11,2]]},"group-title":"Microbiology","reference-count":81,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,11,2]],"date-time":"2024-11-02T00:00:00Z","timestamp":1730505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,11,2]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                  poses a serious challenge for human health, and new antibiotics with novel targets are needed. Here we demonstrate that an acylaminooxadiazole, MBX-4132, specifically inhibits the\n                  <jats:italic>trans<\/jats:italic>\n                  -translation ribosome rescue pathway to kill\n                  <jats:italic>M. tuberculosis<\/jats:italic>\n                  . Our data demonstrate that MBX-4132 is bactericidal against multiple pathogenic mycobacterial species and kills\n                  <jats:italic>M. tuberculosis<\/jats:italic>\n                  in macrophages. We also show that acylaminooxadiazole activity is antagonized by iron but is potentiated by zinc. Our transcriptomic data reveals dysregulation of multiple metal homeostasis pathways after exposure to MBX-4132. Furthermore, we see differential expression of genes related to zinc sensing and efflux when\n                  <jats:italic>trans<\/jats:italic>\n                  -translation is inhibited. Taken together, these data suggest that there is a link between disturbing intracellular metal levels and acylaminooxadiazole-mediated inhibition of\n                  <jats:italic>trans<\/jats:italic>\n                  -translation. These findings provide an important proof-of-concept that\n                  <jats:italic>trans<\/jats:italic>\n                  -translation is a promising antitubercular drug target.\n                <\/jats:p>","DOI":"10.1101\/2024.11.02.621434","type":"posted-content","created":{"date-parts":[[2024,11,2]],"date-time":"2024-11-02T17:40:17Z","timestamp":1730569217000},"source":"Crossref","is-referenced-by-count":0,"title":["A\n                  <i>trans<\/i>\n                  -translation inhibitor is potentiated by zinc and kills\n                  <i>Mycobacterium tuberculosis<\/i>\n                  and non-tuberculous mycobacteria"],"prefix":"10.64898","author":[{"given":"Akanksha","family":"Varshney","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8279-5561","authenticated-orcid":false,"given":"Ziyi","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael D.","family":"Howe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth C.","family":"Keiler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony D.","family":"Baughn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024110602151021000_2024.11.02.621434v1.1","unstructured":"Global tuberculosis report 2023. 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