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We report that Hoechst 33258 exhibits antimicrobial activity against\n            <jats:italic>Pneumocystis carinii<\/jats:italic>\n            f. sp.\n            <jats:italic>muris<\/jats:italic>\n            in a mouse model for\n            <jats:italic>P. carinii<\/jats:italic>\n            pneumonia and against\n            <jats:italic>Candida albicans<\/jats:italic>\n            and\n            <jats:italic>Candida dubliniensis<\/jats:italic>\n            in vitro. Relative to saline treatment, a 14-day, daily treatment of mice with 37.5 mg of Hoechst 33258\/kg of body weight after inoculation with\n            <jats:italic>P. carinii<\/jats:italic>\n            reduced by about 100-fold the number of\n            <jats:italic>P. carinii<\/jats:italic>\n            organisms detected by either PCR or by microscopy after silver staining. For comparison, treatment based on a dose of 15 to 20 mg of the trimethoprim component in trimethoprim-sulfamethoxazole\/kg reduced the number of\n            <jats:italic>P. carinii<\/jats:italic>\n            by about fourfold. In vitro inhibition of\n            <jats:italic>P. carinii<\/jats:italic>\n            group I intron splicing was observed with a 50% inhibitory concentration (IC\n            <jats:sub>50<\/jats:sub>\n            )of 30 \u03bcM in 2 or 4 mM Mg\n            <jats:sup>2+<\/jats:sup>\n            , suggesting RNA as a possible target. However, Hoechst 33258 inhibits growth of\n            <jats:italic>Candida<\/jats:italic>\n            strains with and without group I introns. IC\n            <jats:sub>50<\/jats:sub>\n            s ranged from 1 to 9 \u03bcM for strains with group I introns and were 12 and 32 \u03bcM for two strains without group I introns. These studies demonstrate that compounds that bind fungal nucleic acids have the potential to be developed as new therapeutics for\n            <jats:italic>Pneumocystis<\/jats:italic>\n            and possibly other fungi, especially if they could be directed to structures that are not present in mammalian cells, such as self-splicing introns.\n          <\/jats:p>","DOI":"10.1128\/aac.49.4.1326-1330.2005","type":"journal-article","created":{"date-parts":[[2005,3,25]],"date-time":"2005-03-25T19:23:13Z","timestamp":1111778593000},"page":"1326-1330","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["Activity of Hoechst 33258 against\n            <i>Pneumocystis carinii<\/i>\n            f. sp.\n            <i>muris<\/i>\n            ,\n            <i>Candida albicans<\/i>\n            , and\n            <i>Candida dubliniensis<\/i>"],"prefix":"10.1128","volume":"49","author":[{"given":"Matthew D.","family":"Disney","sequence":"first","affiliation":[{"name":"Department of Chemistry"},{"name":"Center for Human Genetics and Molecular Pediatric Disease"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Stephenson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry W.","family":"Wright","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"},{"name":"Department of Microbiology, School of Medicine and Dentistry, University of Rochester, Rochester, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantine G.","family":"Haidaris","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Medicine and Dentistry, University of Rochester, Rochester, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas H.","family":"Turner","sequence":"additional","affiliation":[{"name":"Department of Chemistry"},{"name":"Center for Human Genetics and Molecular Pediatric Disease"},{"name":"Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Gigliotti","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"},{"name":"Department of Microbiology, School of Medicine and Dentistry, University of Rochester, Rochester, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1093\/nar\/24.8.1460","volume":"24","year":"1996","unstructured":"Bailly, C., P. 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