{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:02:46Z","timestamp":1782280966156,"version":"3.54.5"},"posted":{"date-parts":[[2025,12,15]]},"group-title":"Microbiology","reference-count":71,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,15]]},"abstract":"<jats:p>\n                  The pathogen\n                  <jats:italic>Mycobacterium abscessus<\/jats:italic>\n                  (\n                  <jats:italic>Mab<\/jats:italic>\n                  ) can cause severe and difficult to treat chronic lung infections. Despite the rising incidence and clinical concern of\n                  <jats:italic>Mab<\/jats:italic>\n                  infections, treatment options are limited and often ineffective. Treatment is complicated by\n                  <jats:italic>Mab<\/jats:italic>\n                  \u2019s ability to persist in a non-replicative, drug-resistant state. Several \u03b2-lactam antibiotics are potently bactericidal against\n                  <jats:italic>Mab<\/jats:italic>\n                  but are underutilized because their molecular mechanisms of action against\n                  <jats:italic>Mab<\/jats:italic>\n                  are incompletely understood. In the current study, we used \u03b2-lactam-derived activity-based probes and chemoproteomics to report the first comprehensive list of enzymes in\n                  <jats:italic>Mab<\/jats:italic>\n                  targeted by \u03b2-lactams. We compared \u03b2-lactam targets across two\n                  <jats:italic>Mab<\/jats:italic>\n                  subspecies in actively replicating and non-replicative cultures, using a new carbon starvation model of persistence. We identified 17 targets that were active in every condition tested, seven of which were previously unknown to bind \u03b2-lactams. Lastly, we characterized the \u03b2-lactamase activity and \u03b2-lactam inhibition profiles of nine\n                  <jats:italic>Mab<\/jats:italic>\n                  enzymes, demonstrating that imipenem inhibits these targets more effectively than cefoxitin. These findings provide clarity on the mechanisms of action of clinically relevant \u03b2-lactams in\n                  <jats:italic>Mab<\/jats:italic>\n                  , a crucial step toward fully realizing their potential for treating infections caused by this opportunistic pathogen.\n                <\/jats:p>","DOI":"10.64898\/2025.12.15.694292","type":"posted-content","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T02:55:11Z","timestamp":1765853711000},"source":"Crossref","is-referenced-by-count":0,"title":["Chemoproteomic elucidation of \u03b2-lactam drug targets in\n                  <i>Mycobacterium abscessus<\/i>"],"prefix":"10.64898","author":[{"given":"Kaylyn L.","family":"Devlin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Hutchinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damon 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