{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:10:56Z","timestamp":1790205056782,"version":"4.1.0"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2014,12,1]],"date-time":"2014-12-01T00:00:00Z","timestamp":1417392000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Aminoglycosides exhibit relatively poor activity against intracellular\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Salmonella enterica<\/jats:named-content>\n            serovar Typhimurium due to their low permeativity across eukaryotic cell membranes. Previously, we identified the unique ability of AR-12, a celecoxib-derived small-molecule agent, to eradicate intracellular\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Salmonella<\/jats:named-content>\n            Typhimurium in macrophages by facilitating autophagosome formation and suppressing Akt kinase signaling. In light of this unique mode of antibacterial action, we investigated the ability of AR-12 to sensitize intracellular\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Salmonella<\/jats:named-content>\n            to aminoglycosides in macrophages and in an animal model. The antibacterial activities of AR-12 combined with various aminoglycosides, including streptomycin, kanamycin, gentamicin, and amikacin, against intracellular\n            <jats:italic>S<\/jats:italic>\n            . Typhimurium in murine RAW264.7 macrophages were assessed. Cells were infected with\n            <jats:italic>S<\/jats:italic>\n            . Typhimurium followed by treatment with AR-12 or individual aminoglycosides or with combinations for 24 h. The\n            <jats:italic>in vivo<\/jats:italic>\n            efficacies of AR-12, alone or in combination with gentamicin or amikacin, were also assessed by treating\n            <jats:italic>S<\/jats:italic>\n            . Typhimurium-infected BALB\/c mice daily for 14 consecutive days. Exposure of\n            <jats:italic>S<\/jats:italic>\n            . Typhimurium-infected RAW264.7 cells to a combination of AR-12 with individual aminoglycosides led to a reduction in bacterial survival (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05), both intracellular and extracellular, that was greater than that seen with the aminoglycosides alone. This sensitizing effect, however, was not associated with increased aminoglycoside penetration into bacteria or macrophages. Moreover, daily intraperitoneal injection of AR-12 at 0.1 mg\/kg of body weight significantly increased the\n            <jats:italic>in vivo<\/jats:italic>\n            efficacy of gentamicin and amikacin in prolonging the survival of\n            <jats:italic>S<\/jats:italic>\n            . Typhimurium-infected mice. These findings indicate that the unique ability of AR-12 to enhance the\n            <jats:italic>in vivo<\/jats:italic>\n            efficacy of aminoglycosides might have translational potential for efforts to develop novel strategies for the treatment of salmonellosis.\n          <\/jats:p>","DOI":"10.1128\/aac.03778-14","type":"journal-article","created":{"date-parts":[[2014,9,29]],"date-time":"2014-09-29T22:09:54Z","timestamp":1412028594000},"page":"7375-7382","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":33,"title":["Sensitization of Intracellular Salmonella enterica Serovar Typhimurium to Aminoglycosides\n            <i>In Vitro<\/i>\n            and\n            <i>In Vivo<\/i>\n            by a Host-Targeted Antimicrobial Agent"],"prefix":"10.1128","volume":"58","author":[{"given":"Jung-Hsin","family":"Lo","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel K.","family":"Kulp","sequence":"additional","affiliation":[{"name":"Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Shih","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio, USA"},{"name":"Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Chieh","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr0301088"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.3.6.698"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.10.2.344"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.7.2283-2292.2003"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1099\/00222615-31-1-37"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/15.6.723"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.10.2511"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkt252"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.icb.7100007"},{"key":"e_1_3_2_11_2","first-page":"346","article-title":"The global burden of typhoid fever","volume":"82","author":"Crump JA","year":"2004","unstructured":"CrumpJALubySPMintzED. 2004. 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