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Among these,\n                    <jats:italic>Mycobacterium abscessus<\/jats:italic>\n                    is particularly refractory owing to its extensive array of resistance mechanisms. Here we introduce florfenicol amine (FF-NH\n                    <jats:sub>2<\/jats:sub>\n                    ), a major metabolite of the antibiotic florfenicol, which acts as a prodrug with narrow-spectrum activity against\n                    <jats:italic>M.<\/jats:italic>\n                    \u2009\n                    <jats:italic>abscessus\u2212chelonae<\/jats:italic>\n                    complex species. FF-NH\n                    <jats:sub>2<\/jats:sub>\n                    leverages intrinsic\n                    <jats:italic>M.<\/jats:italic>\n                    \u2009\n                    <jats:italic>abscessus<\/jats:italic>\n                    resistance conferred by the transcription factor WhiB7. It avoids WhiB7-dependent resistance mediated by the\n                    <jats:italic>O<\/jats:italic>\n                    -acetyltransferase Cat and is activated by the WhiB7-dependent\n                    <jats:italic>N<\/jats:italic>\n                    -acetyltransferase Eis2 in a prodrug fashion to generate the active translational inhibitor FF acetyl (FF-ac). FF-NH\n                    <jats:sub>2<\/jats:sub>\n                    induces Eis2 expression through WhiB7, creating a feed-forward bioactivation loop, which increases FF-ac accumulation and antimicrobial action. FF-NH\n                    <jats:sub>2<\/jats:sub>\n                    displays antiresistance properties, can synergize with other antibiotics and mitigates toxicity linked to mammalian mitochondrial ribosome inhibition. Importantly, FF-NH\n                    <jats:sub>2<\/jats:sub>\n                    demonstrated efficacy in a murine model of\n                    <jats:italic>M.<\/jats:italic>\n                    \u2009\n                    <jats:italic>abscessus<\/jats:italic>\n                    infection. These findings suggest intrinsic resistance can be exploited to develop safer and more effective treatments for this pathogen.\n                  <\/jats:p>","DOI":"10.1038\/s41564-025-02147-9","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T10:03:55Z","timestamp":1761818635000},"page":"2875-2891","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prodrug florfenicol amine is activated by intrinsic resistance to target Mycobacterium abscessus"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5862-5212","authenticated-orcid":false,"given":"Gregory 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