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dc.contributor.authorTassanee Lerksuthiraten_US
dc.contributor.authorAreeporn Sangcakulen_US
dc.contributor.authorTassanee Lohnooen_US
dc.contributor.authorWanta Yingyongen_US
dc.contributor.authorThidarat Rujirawaten_US
dc.contributor.authorTheerapong Krajaejunen_US
dc.contributor.otherMahidol University. Faculty of Medicine, Ramathibodi Hospital. Department of Pathologyen_US
dc.contributor.otherMahidol University. Faculty of Science. Multidisciplinary Unit, Molecular Medicine Programen_US
dc.contributor.otherMahidol University. Faculty of Medicine, Ramathibodi Hospital. Research Centeren_US
dc.date.accessioned2021-02-13T17:42:37Z-
dc.date.available2021-02-13T17:42:37Z-
dc.date.created2021-02-14-
dc.date.issued2017-
dc.identifier.citationAntimicrobial Agents and Chemotherapy. Vol.61, No.4 (2017), 1-14en_US
dc.identifier.urihttp://repository.li.mahidol.ac.th/dspace/handle/123456789/61242-
dc.description.abstractPythiosis is a life-threatening infectious disease caused by the oomycete Pythium insidiosum. Direct exposure to Py. insidiosum zoospores can initiate infections of the eye, limb, gastrointestinal tract, or skin/subcutaneous tissue. Treatments for pythiosis have mostly relied on surgery. Antifungal drugs are generally ineffective against Py. insidiosum. However, one patient with an invasive Py. insidiosum infection recovered completely following treatment with terbinafine and itraconazole. Additionally, the drug target sterol biosynthetic enzymes have been identified in the oomycete Aphanomyces euteiches. It remains an open question whether Py. insidiosum is susceptible to the antifungal drugs and harbors any of the known drug target enzymes. Here, we determined the in vitro susceptibilities of terbinafine and itraconazole against 30 isolates of Py. insidiosum. We also analyzed endogenous sterols and searched for genes encoding the sterol biosynthetic enzymes in the genomes of Py. insidiosum and related oomycetes. The susceptibility assay showed that the growth of each of the Py. insidiosum isolates was inhibited by the antifungal agents, but only at difficult-to-achieve concentrations, which explains the clinical resistance of the drugs in the treatment of pythiosis patients. Genome searches of Py. insidiosum and related oomycetes demonstrated that these organisms contained an incomplete set of sterol biosynthetic enzymes. Gas chromatographic mass spectrometry did not detect any sterol end products in Py. insidiosum. In conclusion, Py. insidiosum possesses an incomplete sterol biosynthetic pathway. Resistance to antifungal drugs targeting enzymes in the ergosterol biosynthetic pathway in Py. insidiosum was due to modifications or losses of some of the genes encoding the drug target enzymes.en_US
dc.language.isoen_USen_US
dc.rightsMahidol Universityen_US
dc.subjectPythium insidiosumen_US
dc.subjectPythiosisen_US
dc.subjectSterol biosynthetic enzymeen_US
dc.subjectIn vitro susceptibilityen_US
dc.subjectEvolutionen_US
dc.subjectAntifungal drugen_US
dc.titleEvolution of the Sterol Biosynthetic Pathway of Pythium insidiosum and Related Oomycetes Contributes to Antifungal Drug Resistanceen_US
dc.typeResearch Articleen_US
dc.rights.holderAmerican Society for Microbiologyen_US
dc.identifier.urlhttps://aac.asm.org/content/61/4/e02352-16-
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