{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:25:22Z","timestamp":1792175122390,"version":"4.4.0"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2005,2,1]],"date-time":"2005-02-01T00:00:00Z","timestamp":1107216000000},"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":[[2005,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Rhizopus oryzae<\/jats:italic>\n            is the most common cause of zygomycosis, a life-threatening infection that usually occurs in patients with diabetic ketoacidosis. Despite standard therapy, the overall rate of mortality from zygomycosis remains &gt;50%, and new strategies for treatment are urgently needed. The activities of caspofungin acetate (CAS) and other echinocandins (antifungal inhibitors of the synthesis of 1,3-\u03b2-\n            <jats:sc>d<\/jats:sc>\n            -glucan synthase [GS]) against the agents of zygomycosis have remained relatively unexplored, especially in animal models of infection. We found that\n            <jats:italic>R. oryzae<\/jats:italic>\n            has both an\n            <jats:italic>FKS<\/jats:italic>\n            gene, which in other fungi encodes a subunit of the GS synthesis complex, and CAS-susceptible, membrane-associated GS activity. Low-dose but not high-dose CAS improved the survival of mice with diabetic ketoacidosis infected with a small inoculum but not a large inoculum of\n            <jats:italic>R. oryzae<\/jats:italic>\n            . Fungal burden, assessed by a novel quantitative PCR assay, correlated with increasing inocula and progression of disease, particularly later in the infection, when CFU counts did not. CAS decreased the brain burden of\n            <jats:italic>R. oryzae<\/jats:italic>\n            when it was given prophylactically but not when therapy was started after infection. These results indicate that CAS has significant but limited activity against\n            <jats:italic>R. oryzae<\/jats:italic>\n            in vivo and demonstrates an inverse dose-response effect. The potential for CAS to play a role in combination therapy against zygomycosis merits further investigation.\n          <\/jats:p>","DOI":"10.1128\/aac.49.2.721-727.2005","type":"journal-article","created":{"date-parts":[[2005,1,26]],"date-time":"2005-01-26T22:04:40Z","timestamp":1106777080000},"page":"721-727","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":190,"title":["Caspofungin Inhibits\n            <i>Rhizopus oryzae<\/i>\n            1,3-\u03b2-\n            <scp>d<\/scp>\n            -Glucan Synthase, Lowers Burden in Brain Measured by Quantitative PCR, and Improves Survival at a Low but Not a High Dose during Murine Disseminated Zygomycosis"],"prefix":"10.1128","volume":"49","author":[{"given":"Ashraf S.","family":"Ibrahim","sequence":"first","affiliation":[{"name":"Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles, Medical Center, Torrance"},{"name":"University of California, Los Angeles, School of Medicine, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel C.","family":"Bowman","sequence":"additional","affiliation":[{"name":"Department of Human and Animal Infectious Disease Research, Merck Research Laboratories, Rahway, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Avanessian","sequence":"additional","affiliation":[{"name":"Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles, Medical Center, Torrance"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keturah","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Human and Animal Infectious Disease Research, Merck Research Laboratories, Rahway, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brad","family":"Spellberg","sequence":"additional","affiliation":[{"name":"Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles, Medical Center, Torrance"},{"name":"University of California, Los Angeles, School of Medicine, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"John E.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles, Medical Center, Torrance"},{"name":"University of California, Los Angeles, School of Medicine, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron M.","family":"Douglas","sequence":"additional","affiliation":[{"name":"Department of Human and Animal Infectious Disease Research, Merck Research Laboratories, Rahway, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.9.2310-2318.2000"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.1.245-247.2002"},{"key":"e_1_3_2_4_2","unstructured":"Bowman J. 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