{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:03:06Z","timestamp":1785420186687,"version":"3.56.0"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"26","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22477024"],"award-info":[{"award-number":["22477024"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"MOE | Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Frontier Science Research Base of optogenetic Techniques for Cell Metabolism","award":["grant 2021 Sci & Tech 03-28"],"award-info":[{"award-number":["grant 2021 Sci & Tech 03-28"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,6,30]]},"abstract":"<jats:p>\n                    The rapid global spread of antimicrobial resistance via \u03b2-lactamase (bla) demands targeted strategies that selectively eliminate resistant pathogens without exacerbating resistance. Herein, we report\n                    <jats:bold>BIN-3I<\/jats:bold>\n                    , a photosensitizer (PS) that enables bla-selective activation and\u2014more importantly\u2014covalent retention and accumulation within resistant bacteria, allowing potent photodynamic eradication of bla-expressing pathogens and exerting counter-selection pressure.\n                    <jats:bold>BIN-3I<\/jats:bold>\n                    adopts an enzyme-triggered \"one-to-multi\" design: Upon bla hydrolysis, it undergoes a hydrophilic-to-hydrophobic and low-to-high permeability transition, facilitating uptake and generating a reactive quinone methide intermediate that covalently binds intracellular proteins, leading to &gt;2,000-fold accumulation within resistant bacteria, thiol depletion and light-triggered reactive oxygen species generation. In vitro,\n                    <jats:bold>BIN-3I<\/jats:bold>\n                    demonstrated bla-specific activation, selective enrichment in bla-expressing MRSA, and potent photodynamic killing (&gt;99.999% reduction), outperforming the corresponding uncaged photosensitizer. Crucially, it selectively eradicates bla-producing MRSA within mixed populations, exerting counter-selection pressure against resistant strains. The PS also activates and accumulates in bla-expressing Gram-negative\n                    <jats:italic toggle=\"yes\">Enterobacter cloacae<\/jats:italic>\n                    , albeit with reduced killing efficiency compared to Gram-positive bacteria. In vivo, it exhibited prolonged retention at infection sites and targeted imaging capability in murine myositis and abscess models. Notably,\n                    <jats:bold>BIN-3I<\/jats:bold>\n                    -mediated photodynamic therapy effectively cleared MRSA infections across multiple models\u2014including thigh infection, wound, and biofilm-associated infections\u2014achieving &gt;5-log reduction in bacterial load and surpassing vancomycin in efficacy. This work presents a targeted antimicrobial platform that exploits bacterial resistance mechanisms to achieve species-specific eradication, offering a promising strategy to combat multidrug-resistant infections and alleviate the selection pressure that drives the enrichment of resistant strains.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2536405123","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T18:06:47Z","timestamp":1782238007000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Counterselection against \u03b2-lactamase-expressing bacteria via an activatable photosensitizer that accumulates in resistant pathogens"],"prefix":"10.1073","volume":"123","author":[{"given":"Fangfang","family":"Chen","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01vyrm377","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Bioreactor Engineering, 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