{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:12:59Z","timestamp":1791083579544,"version":"4.1.0"},"reference-count":40,"publisher":"Microbiology Society","issue":"5","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI158706"],"award-info":[{"award-number":["AI158706"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,21]]},"abstract":"<jats:p>\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    and pathogenic nontuberculous mycobacteria pose a growing challenge to human health, and new antibiotics that target new pathways with novel mechanisms of action are urgently needed. Acylaminooxadiazole derivatives have previously been shown to inhibit the\n                    <jats:italic>trans-<\/jats:italic>\n                    translation ribosome rescue pathway and kill\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    . Here, we show that modifications to the acylaminooxadiazole scaffold can improve potency and tune mycobacterial species specificity, resulting in molecules that kill\n                    <jats:italic>Mycobacterium avium<\/jats:italic>\n                    ,\n                    <jats:italic>Mycobacterium abscessus<\/jats:italic>\n                    and\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    clinical isolates. Free iron was previously shown to antagonize antibacterial activity and decrease the inhibition of\n                    <jats:italic>trans<\/jats:italic>\n                    -translation by acylaminooxadiazoles, but we found that biologically relevant iron sources such as haemin and transferrin do not affect activity. Depletion of transfer-messenger RNA resulted in potentiation of acylaminooxadiazole-based\n                    <jats:italic>trans<\/jats:italic>\n                    -translation inhibitors, confirming inhibition of\n                    <jats:italic>trans<\/jats:italic>\n                    -translation as a mechanism of action. Acylaminooxadiazoles disrupted metal homeostasis in\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    , and mutants defective in siderophore-mediated iron utilization were hypersusceptible to some acylaminooxadiazole derivatives, suggesting that these compounds may have a dual mechanism for killing mycobacteria.\n                  <\/jats:p>","DOI":"10.1099\/mic.0.001716","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T16:15:43Z","timestamp":1779380143000},"source":"Crossref","is-referenced-by-count":1,"title":["trans-Translation inhibitors that kill Mycobacterium tuberculosis and pathogenic non-tuberculous mycobacteria also disrupt metal homeostasis"],"prefix":"10.1099","volume":"172","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4524-3523","authenticated-orcid":false,"given":"Akanksha","family":"Varshney","sequence":"first","affiliation":[{"name":"Department of Molecular Biosciences, The University of 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