{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T22:27:04Z","timestamp":1778884024421,"version":"3.51.4"},"reference-count":24,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2015,10,22]],"date-time":"2015-10-22T00:00:00Z","timestamp":1445472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R56 AI070749"],"award-info":[{"award-number":["R56 AI070749"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI070749"],"award-info":[{"award-number":["R01 AI070749"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 AI07509"],"award-info":[{"award-number":["T32 AI07509"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Staphylococcus aureus are Gram-positive bacteria that are the leading cause of recurrent infections in humans that include pneumonia, bacteremia, osteomyelitis, arthritis, endocarditis, and toxic shock syndrome. The emergence of methicillin resistant S. aureus strains (MRSA) has imposed a significant concern in sustained measures of treatment against these infections. Recently, MRSA strains deficient in expression of a serine\/threonine kinase (Stk1 or PknB) were described to exhibit increased sensitivity to \u03b2-lactam antibiotics. In this study, we screened a library consisting of 280 drug-like, low-molecular-weight compounds with the ability to inhibit protein kinases for those that increased the sensitivity of wild-type MRSA to \u03b2-lactams and then evaluated their toxicity in mice. We report the identification of four kinase inhibitors, the sulfonamides ST085384, ST085404, ST085405, and ST085399 that increased sensitivity of WT MRSA to sub-lethal concentrations of \u03b2-lactams. Furthermore, these inhibitors lacked alerting structures commonly associated with toxic effects, and toxicity was not observed with ST085384 or ST085405 in vivo in a murine model. These results suggest that kinase inhibitors may be useful in therapeutic strategies against MRSA infections.<\/jats:p>","DOI":"10.3390\/pathogens4040708","type":"journal-article","created":{"date-parts":[[2015,10,26]],"date-time":"2015-10-26T04:12:04Z","timestamp":1445832724000},"page":"708-721","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Kinase Inhibitors that Increase the Sensitivity of Methicillin Resistant Staphylococcus aureus to \u03b2-Lactam Antibiotics"],"prefix":"10.3390","volume":"4","author":[{"given":"Jay","family":"Vornhagen","sequence":"first","affiliation":[{"name":"Department of Pediatric Infectious Diseases, University of Washington School of Medicine,  Seattle, WA 98195, USA"},{"name":"Seattle Children\u2019s Research Institute, 1900 Ninth Avenue, Seattle, WA 98101, USA"},{"name":"Department of Global Health, University of Washington School of Public Health, Seattle,  WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kellie","family":"Burnside","sequence":"additional","affiliation":[{"name":"Department of Pediatric Infectious Diseases, University of Washington School of Medicine,  Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Whidbey","sequence":"additional","affiliation":[{"name":"Department of Pediatric Infectious Diseases, University of Washington School of Medicine,  Seattle, WA 98195, USA"},{"name":"Seattle Children\u2019s Research Institute, 1900 Ninth Avenue, Seattle, WA 98101, USA"},{"name":"Department of Global Health, University of Washington School of Public Health, Seattle,  WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Berry","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Research Institute, 1900 Ninth Avenue, Seattle, WA 98101, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuan","family":"Qin","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Research Institute, 1900 Ninth Avenue, Seattle, WA 98101, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lakshmi","family":"Rajagopal","sequence":"additional","affiliation":[{"name":"Department of Pediatric Infectious Diseases, University of Washington School of Medicine,  Seattle, WA 98195, USA"},{"name":"Seattle Children\u2019s Research Institute, 1900 Ninth Avenue, Seattle, WA 98101, USA"},{"name":"Department of Global Health, University of Washington School of Public Health, Seattle,  WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Styers, D., Sheehan, D.J., Hogan, P., and Sahm, D.F. 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