{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T01:57:34Z","timestamp":1788487054833,"version":"build-2803163510"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"NIGMS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"name":"COBRE Center for Antimicrobial Resistance and Therapeutic Discovery Pilot project"},{"name":"NSAID","award":["5R01AI141522-04"],"award-info":[{"award-number":["5R01AI141522-04"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Enterococcus faecalis is a common cause of healthcare-associated infections. They characteristically exhibit reduced susceptibility to penicillins and elevated MICs for aminoglycosides, limiting these drugs as single-agent therapies. Combinations of cell wall synthesis inhibitors and aminoglycosides have a synergistic effect, resulting in bactericidal activity. The mechanism behind this synergism is not fully understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The present study was performed to explore the relationship between synergistic activity between cell wall-active agents\/aminoglycoside combinations and cell membrane energetics in E. faecalis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Analysis was performed using reference broth microdilution MIC testing, checkerboard assays, time\u2013kill assays and fluorescent microscopy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We observed that cell wall remodelling agents promoted aminoglycoside uptake facilitated by antibiotic-induced decreases in the intracellular pH (pHi).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Drugs that inhibit cell wall synthesis induce a decrease in the pHi, suggesting that cell wall remodelling is linked to ion transport and cytoplasmic acidification. Our study supports a model in which inhibition of peptidoglycan synthesis produces membrane stress-associated intracellular acidification that promotes \u0394pH-dependent aminoglycoside uptake in E. faecalis<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag210","type":"journal-article","created":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T11:41:16Z","timestamp":1781955676000},"source":"Crossref","is-referenced-by-count":1,"title":["Insights into the mechanisms underlying cell wall-active agents and gentamicin bactericidal synergism against\n                    <i>Enterococcus faecalis<\/i>"],"prefix":"10.1093","volume":"81","author":[{"given":"Paul","family":"Ugalde Silva","sequence":"first","affiliation":[{"name":"Department of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University , Providence, RI ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlene","family":"Desbonnet","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University , Providence, RI ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis B","family":"Rice","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University , Providence, RI ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Garc\u00eda-Solache","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University , Providence, RI ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"2026062303382305800_dkag210-B1","doi-asserted-by":"publisher","first-page":"1556","DOI":"10.1128\/AAC.02001-13","article-title":"Genetic basis for vancomycin-enhanced cephalosporin susceptibility in vancomycin-resistant Enterococci revealed using counterselection with dominant-negative thymidylate synthase","volume":"58","author":"Kristich","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"key":"2026062303382305800_dkag210-B2","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1093\/jac\/25.4.551","article-title":"Synergy between penicillin and gentamicin against enterococci","volume":"25","author":"Winstanley","year":"1990","journal-title":"J Antimicrob Chemother"},{"key":"2026062303382305800_dkag210-B3","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1001\/jama.1973.03220090050011","article-title":"Penicillin and gentamicin therapy for Enterococcal infections","volume":"223","author":"Weinstein","year":"1973","journal-title":"JAMA"},{"key":"2026062303382305800_dkag210-B4","doi-asserted-by":"publisher","first-page":"1174","DOI":"10.1136\/jcp.32.11.1174","article-title":"Action and interaction of penicillin and gentamicin on enterococci","volume":"32","author":"Soriano","year":"1979","journal-title":"J Clin Pathol"},{"key":"2026062303382305800_dkag210-B5","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1086\/367661","article-title":"Combination antibiotic therapy for infective Endocarditis","volume":"36","author":"Goldstein","year":"2003","journal-title":"Clin Infect Dis"},{"key":"2026062303382305800_dkag210-B6","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1093\/infdis\/124.6.581","article-title":"Penicillin combined with gentamicin or streptomycin: synergism against Enterococci","volume":"124","author":"Watanakunakorn","year":"1971","journal-title":"J Infect Dis"},{"key":"2026062303382305800_dkag210-B7","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1161\/CIRCULATIONAHA.113.002431","article-title":"A new era for treating Enterococcus faecalis Endocarditis","volume":"127","author":"Miro","year":"2013","journal-title":"Circulation"},{"key":"2026062303382305800_dkag210-B8","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1093\/cid\/ciy064","article-title":"A review of combination antimicrobial therapy for Enterococcus faecalis Bloodstream infections and infective endocarditis","volume":"67","author":"Beganovic","year":"2018","journal-title":"Clin Infect Dis"},{"key":"2026062303382305800_dkag210-B9","doi-asserted-by":"publisher","first-page":"2580","DOI":"10.1172\/JCI106758","article-title":"Studies on antibiotic syngerism against enterococci. 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