Yanxi Yang, , , Shelby Vexler, , , Maria C. Jordan, , , Serena Abbondante, , , Dayeon Kang, , , Huan Peng, , , Michaela Marshall, , , Bita V. Naini, , , Saumya Jain, , , Yei-Chen Lai, , , Nasim Annabi, , , Kenneth P. Roos, , , Eric Pearlman, , and , Irene A. Chen*,
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PMB-M13<sup>αLPS</sup> reduced the minimum inhibitory concentration <i>in vitro</i> by ∼2 orders of magnitude across multiple pathogen strains. Immunocompetent mice with multidrug-resistant <i>P. aeruginosa</i> pneumonia or corneal infection were effectively treated by PMB-M13<sup>αLPS</sup>, which showed potency ∼2 orders of magnitude greater <i>in vivo</i> compared to that of PMB. PMB-M13<sup>αLPS</sup> was well-tolerated, with no toxic effects. Conjugates of antimicrobial peptides and synthetic phages combine engineerable targeting with large payload capacity, improving potency and therapeutic index for otherwise toxic molecules.</p><p >A phage-peptide conjugate delivers an effective but toxic peptide specifically to bacterial cells. The conjugate treated mouse models of infection safely, showing how to increase clinical utility.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 9","pages":"1715–1735"},"PeriodicalIF":10.4000,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00562","citationCount":"0","resultStr":"{\"title\":\"A Synthetic Phage-Peptide Conjugate as a Potent Antibacterial Agent for Pseudomonas aeruginosa Infections\",\"authors\":\"Yanxi Yang, , , Shelby Vexler, , , Maria C. Jordan, , , Serena Abbondante, , , Dayeon Kang, , , Huan Peng, , , Michaela Marshall, , , Bita V. Naini, , , Saumya Jain, , , Yei-Chen Lai, , , Nasim Annabi, , , Kenneth P. Roos, , , Eric Pearlman, , and , Irene A. 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A Synthetic Phage-Peptide Conjugate as a Potent Antibacterial Agent for Pseudomonas aeruginosa Infections
Antibiotic resistance among Gram-negative organisms is a major challenge. Some molecules, including antimicrobial peptides such as polymyxin B (PMB), are antibacterial but toxic due to low specificity, causing poor clinical utility. Drug delivery to bacterial cells using a biocompatible nanomaterial is a possible approach to securing such drugs. We engineered a nonlytic phage to recognize the lipopolysaccharide of Gram-negative bacteria and cross-linked thousands of peptides per virion, making “PMB-M13αLPS”. PMB-M13αLPS reduced the minimum inhibitory concentration in vitro by ∼2 orders of magnitude across multiple pathogen strains. Immunocompetent mice with multidrug-resistant P. aeruginosa pneumonia or corneal infection were effectively treated by PMB-M13αLPS, which showed potency ∼2 orders of magnitude greater in vivo compared to that of PMB. PMB-M13αLPS was well-tolerated, with no toxic effects. Conjugates of antimicrobial peptides and synthetic phages combine engineerable targeting with large payload capacity, improving potency and therapeutic index for otherwise toxic molecules.
A phage-peptide conjugate delivers an effective but toxic peptide specifically to bacterial cells. The conjugate treated mouse models of infection safely, showing how to increase clinical utility.
期刊介绍:
ACS Central Science publishes significant primary reports on research in chemistry and allied fields where chemical approaches are pivotal. As the first fully open-access journal by the American Chemical Society, it covers compelling and important contributions to the broad chemistry and scientific community. "Central science," a term popularized nearly 40 years ago, emphasizes chemistry's central role in connecting physical and life sciences, and fundamental sciences with applied disciplines like medicine and engineering. The journal focuses on exceptional quality articles, addressing advances in fundamental chemistry and interdisciplinary research.