{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T05:44:15Z","timestamp":1778996655223,"version":"3.51.4"},"reference-count":25,"publisher":"Microbiology Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,9,1]]},"abstract":"<jats:p>The shortage of drugs active against meticillin-resistant<jats:italic>Staphylococcus aureus<\/jats:italic>(MRSA) is a growing clinical problem.<jats:italic>In vitro<\/jats:italic>studies indicate that the phenothiazine thioridazine (TZ) might enhance the activity of the \u03b2-lactam antibiotic dicloxacillin (DCX) to a level where MRSA is killed, but experiments in simple animal models have not been performed. In the present study, we introduced<jats:italic>Caenorhabditis elegans<\/jats:italic>infected by<jats:italic>S. aureus<\/jats:italic>as an<jats:italic>in vivo<\/jats:italic>model to test the effect of TZ as a helper drug in combination with DCX. Because TZ is an anthelmintic, initial experiments were carried out to define the thresholds of toxicity, determined by larval development, and induction of stress-response markers. No measurable effects were seen at concentrations of less than 64 mg TZ l<jats:sup>\u22121<\/jats:sup>. Seven different MRSA strains were tested for pathogenicity against<jats:italic>C. elegans<\/jats:italic>, and the most virulent strain (ATCC 33591) was selected for further analyses. In a final experiment, full-grown<jats:italic>C. elegans<\/jats:italic>were exposed to the test strain for 3 days and subsequently treated with 8 mg DCX l<jats:sup>\u22121<\/jats:sup>and 8 mg TZ l<jats:sup>\u22121<\/jats:sup>for 2 days. This resulted in a 14-fold reduction in the intestinal MRSA load as compared with untreated controls. Each drug alone resulted in a two- to threefold reduction in MRSA load. In conclusion,<jats:italic>C. elegans<\/jats:italic>can be used as a simple model to test synergy between DCX and TZ against MRSA. The previously demonstrated<jats:italic>in vitro<\/jats:italic>synergy can be reproduced<jats:italic>in vivo<\/jats:italic>.<\/jats:p>","DOI":"10.1099\/jmm.0.071837-0","type":"journal-article","created":{"date-parts":[[2014,6,10]],"date-time":"2014-06-10T07:11:25Z","timestamp":1402384285000},"page":"1174-1180","source":"Crossref","is-referenced-by-count":11,"title":["Combination therapy with thioridazine and dicloxacillin combats meticillin-resistant Staphylococcus aureus infection in Caenorhabditis elegans"],"prefix":"10.1099","volume":"63","author":[{"given":"Marianne \u00d8.","family":"Poulsen","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark"},{"name":"Institute of Clinical Research, Research Unit of Clinical Microbiology, University of Southern Denmark, Odense, 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