Medicinal genetics approach towards identifying the molecular target of a novel inhibitor of fungal cell wall assembly
| العنوان: | Medicinal genetics approach towards identifying the molecular target of a novel inhibitor of fungal cell wall assembly |
|---|---|
| المؤلفون: | Kentaro Yoshimatsu, Yoshifumi Jigami, Junko Kai, Kazutaka Nakamoto, Junro Kuromitsu, Katsura Hata, Naoaki Watanabe, Mamiko Tsuchiya, Takeshi Nagasu, Koji Sagane, Fuminori Ohba, Kappei Tsukahara |
| المصدر: | Molecular Microbiology. 48:1029-1042 |
| بيانات النشر: | Wiley, 2003. |
| سنة النشر: | 2003 |
| مصطلحات موضوعية: | Genetics, biology, Cell, Saccharomyces cerevisiae, Mutant, biology.organism_classification, Microbiology, carbohydrates (lipids), Gene product, Cell wall, medicine.anatomical_structure, medicine, Target protein, Candida albicans, Molecular Biology, Gene |
| الوصف: | Glycosylphosphatidylinositol (GPI)-anchored cell wall mannoproteins are required for the adhesion of pathogenic fungi, such as Candida albicans, to human epithelium. Small molecular inhibitors of the cell surface presentation of GPI-anchored mannoproteins would be promising candidate drugs to block the establishment of fungal infections. Here, we describe a medicinal genetics approach to identifying the gene encoding a novel target protein that is required for the localization of GPI-anchored cell wall mannoproteins. By means of a yeast cell-based screening procedure, we discovered a compound, 1-[4-butylbenzyl]isoquinoline (BIQ), that inhibits cell wall localization of GPI-anchored mannoproteins in Saccharomyces cerevisiae. Treatment of C. albicans cells with this compound resulted in reduced adherence to a rat intestine epithelial cell monolayer. A previously uncharacterized gene YJL091c, named GWT1, was cloned as a dosage-dependent suppressor of the BIQ-induced phenotypes. GWT1 knock-out cells showed similar phenotypes to BIQ-treated wild-type cells in terms of cell wall structure and transcriptional profiles. Two different mutants resistant to BIQ each contained a single missense mutation in the coding region of the GWT1 gene. These results all suggest that the GWT1 gene product is the primary target of the compound. |
| تدمد: | 1365-2958 0950-382X |
| DOI: | 10.1046/j.1365-2958.2003.03481.x |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::6e93d7cb1d94e0bf41f18bd69dfe5bff https://doi.org/10.1046/j.1365-2958.2003.03481.x |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi...........6e93d7cb1d94e0bf41f18bd69dfe5bff |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13652958 0950382X |
|---|---|
| DOI: | 10.1046/j.1365-2958.2003.03481.x |