{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,22]],"date-time":"2025-03-22T10:53:39Z","timestamp":1742640819110,"version":"3.37.3"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,4,2]],"date-time":"2019-04-02T00:00:00Z","timestamp":1554163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K24-AI121296","R01-AI134637","R01-AI093749","R21 AI121519","R01AI076406","R01AI110432","R01 AI080714"],"award-info":[{"award-number":["K24-AI121296","R01-AI134637","R01-AI093749","R21 AI121519","R01AI076406","R01AI110432","R01 AI080714"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Daptomycin resistance in enterococci is often mediated by the LiaFSR system, which orchestrates the cell membrane stress response. Activation of LiaFSR through the response regulator LiaR generates major changes in cell membrane function and architecture (membrane adaptive response), permitting the organism to survive the antibiotic attack. Here, using a laboratory strain of Enterococcus faecalis, we developed a novel Caenorhabditis elegans model of daptomycin therapy and showed that disrupting LiaR-mediated cell membrane adaptation restores the in vivo activity of daptomycin. The LiaR effect was also seen in a clinical strain of daptomycin-resistant Enterococcus faecium, using a murine model of peritonitis. Furthermore, alteration of the cell membrane response increased the ability of human polymorphonuclear neutrophils to readily clear both E. faecalis and multidrug-resistant E. faecium. Our results provide proof of concept that targeting the cell membrane adaptive response restores the in vivo activity of antibiotics, prevents resistance, and enhances the ability of the innate immune system to kill infecting bacteria.<\/jats:p>","DOI":"10.1093\/infdis\/jiz131","type":"journal-article","created":{"date-parts":[[2019,3,22]],"date-time":"2019-03-22T20:14:50Z","timestamp":1553285690000},"page":"494-504","source":"Crossref","is-referenced-by-count":7,"title":["Disrupting Membrane Adaptation Restores In Vivo Efficacy of Antibiotics Against Multidrug-Resistant Enterococci and Potentiates Killing by Human Neutrophils"],"prefix":"10.1093","volume":"220","author":[{"given":"Sandra","family":"Rincon","sequence":"first","affiliation":[{"name":"Center for Antimicrobial Resistance and Microbial Genomics, Rice University"},{"name":"Molecular Genetics and Antimicrobial Resistance Unit and International Center for Microbial Genomics, Universidad El Bosque, Bogota, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana","family":"Panesso","sequence":"additional","affiliation":[{"name":"Center for Antimicrobial Resistance and Microbial Genomics, Rice University"},{"name":"Department of Internal Medicine, Division of Infectious Diseases, Rice University"},{"name":"Molecular Genetics and Antimicrobial Resistance Unit and International Center for Microbial Genomics, Universidad El Bosque, Bogota, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William R","family":"Miller","sequence":"additional","affiliation":[{"name":"Center for Antimicrobial Resistance and Microbial Genomics, Rice University"},{"name":"Department of Internal Medicine, Division of Infectious Diseases, Rice University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kavindra V","family":"Singh","sequence":"additional","affiliation":[{"name":"Center for Antimicrobial Resistance and Microbial Genomics, Rice University"},{"name":"Department of Internal Medicine, Division of Infectious Diseases, Rice University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa R","family":"Cruz","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, UTHealth McGovern Medical School, Rice University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayesha","family":"Khan","sequence":"additional","affiliation":[{"name":"Center for Antimicrobial Resistance and Microbial Genomics, Rice University"},{"name":"Department of Microbiology and Molecular Genetics, UTHealth McGovern Medical School, Rice University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"An Q","family":"Dinh","sequence":"additional","affiliation":[{"name":"Center for Antimicrobial Resistance and Microbial Genomics, Rice University"},{"name":"Department of Internal Medicine, Division of Infectious Diseases, Rice University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorena","family":"Diaz","sequence":"additional","affiliation":[{"name":"Center for Antimicrobial Resistance and Microbial Genomics, Rice University"},{"name":"Molecular Genetics and Antimicrobial Resistance Unit and International Center for Microbial Genomics, Universidad El Bosque, Bogota, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Rios","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Antimicrobial Resistance Unit and International Center for Microbial Genomics, Universidad El Bosque, Bogota, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yousif","family":"Shamoo","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Rice University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinnethe","family":"Reyes","sequence":"additional","affiliation":[{"name":"Center for Antimicrobial Resistance and Microbial Genomics, Rice University"},{"name":"Molecular Genetics and Antimicrobial Resistance Unit and International Center for Microbial Genomics, Universidad El Bosque, Bogota, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Truc T","family":"Tran","sequence":"additional","affiliation":[{"name":"Center for Antimicrobial Resistance and Microbial Genomics, Rice University"},{"name":"Department of Internal Medicine, Division of Infectious Diseases, Rice University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle A","family":"Garsin","sequence":"additional","affiliation":[{"name":"Center for Antimicrobial Resistance and Microbial Genomics, Rice University"},{"name":"Department of Microbiology and Molecular Genetics, UTHealth McGovern Medical School, Rice University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cesar A","family":"Arias","sequence":"additional","affiliation":[{"name":"Center for Antimicrobial Resistance and Microbial Genomics, Rice University"},{"name":"Department of Internal Medicine, Division of Infectious Diseases, Rice University"},{"name":"Department of Microbiology and Molecular Genetics, UTHealth McGovern Medical School, Rice University"},{"name":"Center for Infectious Diseases, School of Public Health, University of Texas Health Science Center, Houston, Texas"},{"name":"Molecular Genetics and Antimicrobial Resistance Unit and International Center for Microbial Genomics, Universidad El Bosque, Bogota, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,4,2]]},"reference":[{"key":"2019070205530564600_CIT0001","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1128\/AAC.27.3.357","article-title":"In vitro activity and mechanism of action of A21978C1, a novel cyclic lipopeptide antibiotic","volume":"27","author":"Eliopoulos","year":"1985","journal-title":"Antimicrob Agents 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