{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T10:25:33Z","timestamp":1789208733291,"version":"build-2803163510"},"reference-count":20,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2011,9,1]],"date-time":"2011-09-01T00:00:00Z","timestamp":1314835200000},"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":[[2011,9]]},"abstract":"ABSTRACT<\/jats:title>\n \n We investigated the cellular mechanisms responsible for the occurrence of miconazole-tolerant persisters in\n Candida albicans<\/jats:named-content>\n biofilms. Miconazole induced about 30% killing of sessile\n C. albicans<\/jats:named-content>\n cells at 75 \u03bcM. The fraction of miconazole-tolerant persisters, i.e., cells that can survive high doses of miconazole (0.6 to 2.4 mM), in these biofilms was 1 to 2%. Since miconazole induces reactive oxygen species (ROS) in sessile\n C. albicans<\/jats:named-content>\n cells, we focused on a role for superoxide dismutases (Sods) in persistence and found the expression of Sod-encoding genes in sessile\n C. albicans<\/jats:named-content>\n cells induced by miconazole compared to the expression levels in untreated sessile\n C. albicans<\/jats:named-content>\n cells. Moreover, addition of the superoxide dismutase inhibitor\n N<\/jats:italic>\n ,\n N<\/jats:italic>\n \u2032-diethyldithiocarbamate (DDC) to\n C. albicans<\/jats:named-content>\n biofilms resulted in an 18-fold reduction of the miconazole-tolerant persister fraction and in increased endogenous ROS levels in these cells. Treatment of biofilms of\n C. albicans<\/jats:named-content>\n clinical isolates with DDC resulted in an 18-fold to more than 200-fold reduction of their miconazole-tolerant persister fraction. To further confirm the important role for Sods in\n C. albicans<\/jats:named-content>\n biofilm persistence, we used a \u0394\n sod4<\/jats:italic>\n \u0394\n sod5<\/jats:italic>\n mutant lacking Sods 4 and 5. Biofilms of the \u0394\n sod4<\/jats:italic>\n \u0394\n sod5<\/jats:italic>\n mutant contained at least 3-fold less of the miconazole-tolerant persisters and had increased ROS levels compared to biofilms of the isogenic wild type (WT). In conclusion, the occurrence of miconazole-tolerant persisters in\n C. albicans<\/jats:named-content>\n biofilms is linked to the ROS-detoxifying activity of Sods. Moreover, Sod inhibitors can be used to potentiate the activity of miconazole against\n C. albicans<\/jats:named-content>\n biofilms.\n <\/jats:p>","DOI":"10.1128\/aac.00280-11","type":"journal-article","created":{"date-parts":[[2011,7,12]],"date-time":"2011-07-12T06:10:11Z","timestamp":1310451011000},"page":"4033-4037","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":110,"title":["Superoxide Dismutases Are Involved in Candida albicans Biofilm Persistence against Miconazole"],"prefix":"10.1128","volume":"55","author":[{"given":"Anna","family":"Bink","sequence":"first","affiliation":[{"name":"Centre of Microbial and Plant Genetics, CMPG, Katholieke Universiteit Leuven, 3001 Heverlee, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davy","family":"Vandenbosch","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutical Microbiology, LFM, Universiteit Gent, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Coenye","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutical Microbiology, LFM, Universiteit Gent, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Nelis","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmaceutical Microbiology, LFM, Universiteit Gent, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno P. 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