{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:40:34Z","timestamp":1791841234990,"version":"4.3.4"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2015,11,17]],"date-time":"2015-11-17T00:00:00Z","timestamp":1447718400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"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":[[2015,12]]},"abstract":"ABSTRACT<\/jats:title>\n \n This study investigated the antibacterial activity of the plant alkaloid tomatidine (TO) against\n Staphylococcus aureus<\/jats:named-content>\n grown in the presence of\n Pseudomonas aeruginosa<\/jats:named-content>\n . Since the\n P. aeruginosa<\/jats:named-content>\n exoproduct 4-hydroxy-2-heptylquinoline-\n N<\/jats:italic>\n -oxide (HQNO) is known to cause a respiratory deficiency in\n S. aureus<\/jats:named-content>\n and respiratory-deficient\n S. aureus<\/jats:named-content>\n are known to be hypersensitive to TO, we assessed kill kinetics of TO (8 \u03bcg\/ml) against\n S. aureus<\/jats:named-content>\n in coculture with\n P. aeruginosa<\/jats:named-content>\n . Kill kinetics were also assessed using\n P. aeruginosa<\/jats:named-content>\n mutants deficient in the production of different exoproducts and quorum sensing-related compounds. After 24 h in coculture, TO increased the killing of\n S. aureus<\/jats:named-content>\n by 3.4 log\n 10<\/jats:sub>\n CFU\/ml in comparison to that observed in a coculture without TO. The effect of TO was abolished when\n S. aureus<\/jats:named-content>\n was in coculture with the\n lasR<\/jats:italic>\n rhlR<\/jats:italic>\n ,\n pqsA<\/jats:italic>\n ,\n pqsL<\/jats:italic>\n , or\n lasA<\/jats:italic>\n mutant of\n P. aeruginosa<\/jats:named-content>\n . The bactericidal effect of TO against\n S. aureus<\/jats:named-content>\n in coculture with the\n pqsL<\/jats:italic>\n mutant was restored by supplemental HQNO. In an\n S. aureus<\/jats:named-content>\n monoculture, the combination of HQNO and TO was bacteriostatic, indicating that the\n pqsL<\/jats:italic>\n mutant produced an additional factor required for the bactericidal effect. The bactericidal activity of TO was also observed against a tobramycin-resistant methicillin-resistant\n S. aureus<\/jats:named-content>\n (MRSA) in coculture with\n P. aeruginosa<\/jats:named-content>\n , and the addition of tobramycin significantly suppressed the growth of both microorganisms. TO shows a strong bactericidal effect against\n S. aureus<\/jats:named-content>\n when cocultured with\n P. aeruginosa<\/jats:named-content>\n . The combination of TO and tobramycin may represent a new treatment approach for cystic fibrosis patients frequently cocolonized by MRSA and\n P. aeruginosa<\/jats:named-content>\n .\n <\/jats:p>","DOI":"10.1128\/aac.01711-15","type":"journal-article","created":{"date-parts":[[2015,9,21]],"date-time":"2015-09-21T22:23:49Z","timestamp":1442874229000},"page":"7458-7464","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":25,"title":["Bactericidal Effect of Tomatidine-Tobramycin Combination against Methicillin-Resistant Staphylococcus aureus and Pseudomonas aeruginosa Is Enhanced by Interspecific Small-Molecule Interactions"],"prefix":"10.1128","volume":"59","author":[{"given":"Simon","family":"Boulanger","sequence":"first","affiliation":[{"name":"Centre d'\u00c9tude et de Valorisation de la Diversit\u00e9 Microbienne (CEVDM), D\u00e9partement de biologie, Facult\u00e9 des sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Centre d'\u00c9tude et de Valorisation de la Diversit\u00e9 Microbienne (CEVDM), D\u00e9partement de biologie, Facult\u00e9 des sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamal","family":"Bouarab","sequence":"additional","affiliation":[{"name":"Centre d'\u00c9tude et de Valorisation de la Diversit\u00e9 Microbienne (CEVDM), D\u00e9partement de biologie, Facult\u00e9 des sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9ric","family":"Marsault","sequence":"additional","affiliation":[{"name":"D\u00e9partement de pharmacologie, Facult\u00e9 de m\u00e9decine et des sciences de la sant\u00e9, Universit\u00e9 de Sherbrooke, Sherbrooke, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Cantin","sequence":"additional","affiliation":[{"name":"D\u00e9partement de m\u00e9decine, Facult\u00e9 de m\u00e9decine et des sciences de la sant\u00e9, Universit\u00e9 de Sherbrooke, Sherbrooke, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric H.","family":"Frost","sequence":"additional","affiliation":[{"name":"D\u00e9partement de microbiologie et infectiologie, Facult\u00e9 de m\u00e9decine et des sciences de la sant\u00e9, Universit\u00e9 de Sherbrooke, Sherbrooke, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"D\u00e9ziel","sequence":"additional","affiliation":[{"name":"INRS-Institut Armand-Frappier, Laval, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Malouin","sequence":"additional","affiliation":[{"name":"Centre d'\u00c9tude et de Valorisation de la Diversit\u00e9 Microbienne (CEVDM), D\u00e9partement de biologie, Facult\u00e9 des sciences, Universit\u00e9 de Sherbrooke, Sherbrooke, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.75.103004.142532"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.15.2.194-222.2002"},{"key":"e_1_3_2_4_2","volume-title":"Cystic fibrosis patient registry, 2012 annual data report","author":"Cystic Fibrosis Foundation USA","year":"2013","unstructured":"Cystic Fibrosis Foundation USA. 2013. 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