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We investigate whether tetracyclines inhibit LasB by computational modeling and biochemical assays, then examined their efficacy in model infections with human neutrophils in vitro and in a murine pulmonary model. Tetracycline, doxycycline, minocycline, and tigecycline all inhibited LasB proteolysis, while other relevant antibiotics did not. At subantimicrobial concentrations, tetracyclines sensitized Pseudomonas to neutrophil killing and significantly reduced lung pathology, even for multidrug-resistant strains. By controlling pathological host responses, inhibiting bacterial virulence factors, and facilitating bacterial killing, tetracyclines can thus have tripartite therapeutic benefits.<\/jats:p>","DOI":"10.1093\/infdis\/jiaf355","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T07:53:10Z","timestamp":1751615590000},"page":"e416-e420","source":"Crossref","is-referenced-by-count":1,"title":["Therapeutic Inhibition of Metalloproteases by Tetracyclines During Infection by Multidrug-Resistant\n                    <i>Pseudomonas<\/i>"],"prefix":"10.1093","volume":"232","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7157-393X","authenticated-orcid":false,"given":"Mary A","family":"Carr","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine , Atlanta, Georgia 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Atlanta, Georgia ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3035-5331","authenticated-orcid":false,"given":"Christopher N","family":"LaRock","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine , Atlanta, Georgia ,","place":["USA"]},{"name":"Department of Medicine, Division of Infectious Disease, Emory University School of Medicine , Atlanta, Georgia ,","place":["USA"]},{"name":"Antimicrobial Resistance Center, Emory University , Atlanta, Georgia ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"key":"2025092306164283200_jiaf355-B1","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1164\/rccm.201705-1043SO","article-title":"Mechanisms and targeted therapies for Pseudomonas aeruginosa lung 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