{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T09:46:03Z","timestamp":1761126363146},"reference-count":30,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2002,5,1]],"date-time":"2002-05-01T00:00:00Z","timestamp":1020211200000},"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":[[2002,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Several chemically modified tetracycline analogs (CMTs), which were chemically modified to eliminate their antibacterial efficacy, were unexpectedly found to have antifungal properties. Of 10 CMTs screened in vitro, all exhibited antifungal activities, although their efficacies varied. Among these compounds, CMT-315, -3, and -308 were found to be the most potent as antifungal agents. The MICs of CMT-3 against 47 strains of fungi in vitro were determined by using amphotericin B (AMB) and doxycycline as positive and negative controls, respectively. The MICs of CMT-3 were generally found to be between 0.25 and 8.00 \u03bcg\/ml, a range that approximates the blood levels of this drug when administrated orally to humans. Of all the yeast species tested to date,\n            <jats:italic>Candida albicans<\/jats:italic>\n            showed the greatest sensitivity to CMT-3. The filamentous species most susceptible to CMT-3 were found to be\n            <jats:italic>Epidermophyton floccosum<\/jats:italic>\n            ,\n            <jats:italic>Microsporum gypseum<\/jats:italic>\n            ,\n            <jats:italic>Pseudallescheria boydii<\/jats:italic>\n            , a\n            <jats:italic>Penicillium<\/jats:italic>\n            sp.,\n            <jats:italic>Scedosporium apiospermum<\/jats:italic>\n            , a\n            <jats:italic>Tricothecium<\/jats:italic>\n            sp., and\n            <jats:italic>Trichophyton rubrum<\/jats:italic>\n            . Growth inhibition of\n            <jats:italic>C. albicans<\/jats:italic>\n            by CMT-3, determined by a turbidity assay, indicated a 50% inhibitory concentration of 1 \u03bcg\/ml. Thirty-nine strains, including 20 yeasts and 19 molds, were used to measure viability (the ability to grow after treatment with a drug) inhibition by CMT-3 and AMB. CMT-3 exhibited fungicidal activity against most of these fungi, especially the filamentous fungi. Eighty-four percent (16 of 19) of the filamentous fungi tested showed more than 90% inhibition of viability by CMT-3. In contrast, AMB showed fungicidal activity against all yeasts tested. However, most of the filamentous fungi (16 of 19) showed less than 50% inhibition of viability by AMB, indicating that AMB is fungistatic against most of these filamentous fungi. To begin to identify the sites in fungal cells affected by CMT-3,\n            <jats:italic>C. albicans<\/jats:italic>\n            and a\n            <jats:italic>Penicillium<\/jats:italic>\n            sp. were incubated with the compound at 35\u00b0C, and then the fluorescence of CMT-3 was observed by confocal laser scanning electron microscopy. CMT-3 appeared to have widespread intracellular distribution throughout\n            <jats:italic>C. albicans<\/jats:italic>\n            and the\n            <jats:italic>Penicillium<\/jats:italic>\n            sp. The mechanisms of the antifungal activity of CMT-3 are now being explored.\n          <\/jats:p>","DOI":"10.1128\/aac.46.5.1447-1454.2002","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:09:01Z","timestamp":1027764541000},"page":"1447-1454","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["A Chemically Modified Tetracycline (CMT-3) Is a New Antifungal Agent"],"prefix":"10.1128","volume":"46","author":[{"given":"Yu","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Oral Biology and Pathology, School of Dental Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria E.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Pathology, School of Dental Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsi-Ming","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Pathology, School of Dental Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanford","family":"Simon","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Tortora","sequence":"additional","affiliation":[{"name":"Department of Laboratories, University Hospital and Medical Center, State University of New York at Stony Brook, Stony Brook, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol","family":"Lauzon","sequence":"additional","affiliation":[{"name":"School of Sciences, California State University, Hayward, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael K.","family":"Leung","sequence":"additional","affiliation":[{"name":"School of Sciences, California State University, Hayward, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorne M.","family":"Golub","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Pathology, School of Dental Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4157(86)90002-X"},{"key":"e_1_3_1_3_2","doi-asserted-by":"crossref","first-page":"5-22N","DOI":"10.1016\/0002-9343(90)90433-E","volume":"88","year":"1990","unstructured":"Clements, J. 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