Aspergillus nidulans galactofuranose biosynthesis affects antifungal drug sensitivity |
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| Authors: | Md Kausar Alam Amira M El-Ganiny Sharmin Afroz David AR Sanders Juxin Liu Susan GW Kaminskyj |
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| Institution: | 1. Department of Biology, University of Saskatchewan, 112 Science Place, Saskatoon, SK, Canada S7N 5E2;2. Department of Microbiology, Faculty of Pharmacy, Zagazig University, Egypt;3. Department of Chemistry, University of Saskatchewan, 110 Science Place, Saskatoon, SK, Canada S7N 5C9;4. Department of Mathematics and Statistics, University of Saskatchewan, 106 Wiggins Road, Saskatoon, SK, Canada S7N 5E6;1. Department of Microbiology & Immunology, Georgetown University Medical Center, Washington, DC 20057, United States;2. Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences & Technology, Wuhan 430030, China;3. Department of Pathology and Pathophysiology, Shantou University Medical College, Shantou, China;3. Department of Bioscience and Biotechnology, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan;4. ASPEX division, Research Center, Asahi Glass Co., Ltd., 1150 Hazawa-cho, Kanagawa-ku, Yokohama 221-8755, Japan;5. International Center for Biotechnology, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan;1. Industrial Technology Center of Okayama Prefecture, 5301 Haga, Kita-ku, Okayama 701-1296, Japan;2. Department of Bioindustrial Informatics and Genomics, Graduate School of Agricultural Sciences, Tohoku University, 1-1 Tsutsumidori-Amamiya-machi, Aoba-ku, Sendai 981-8555, Japan;3. Fujiwara Techno-Art, 2827-3 Tomiyoshi, Kita-ku, Okayama 701-1133, Japan;1. INBIOTEC, Instituto de Biotecnología de León, Avda. Real n°. 1, Parque Científico de León, 24006 León, Spain;2. Área de Microbiología, Departamento de Biología Molecular, Universidad de León, Campus de Vegazana s/n, 24071 León, Spain |
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| Abstract: | The cell wall is essential for fungal survival in natural environments. Many fungal wall carbohydrates are absent from humans, so they are a promising source of antifungal drug targets. Galactofuranose (Galf) is a sugar that decorates certain carbohydrates and lipids. It comprises about 5% of the Aspergillus fumigatus cell wall, and may play a role in systemic aspergillosis. We are studying Aspergillus wall formation in the tractable model system, A. nidulans. Previously we showed single-gene deletions of three sequential A. nidulans Galf biosynthesis proteins each caused similar hyphal morphogenesis defects and 500-fold reduced colony growth and sporulation. Here, we generated ugeA, ugmA and ugtA strains controlled by the alcA(p) or niiA(p) regulatable promoters. For repression and expression, alcA(p)-regulated strains were grown on complete medium with glucose or threonine, whereas niiA(p)-regulated strains were grown on minimal medium with ammonium or nitrate. Expression was assessed by qPCR and colony phenotype. The alcA(p) and niiA(p) strains produced similar effects: colonies resembling wild type for gene expression, and resembling deletion strains for gene repression. Galf immunolocalization using the L10 monoclonal antibody showed that ugmA deletion and repression phenotypes correlated with loss of hyphal wall Galf. None of the gene manipulations affected itraconazole sensitivity, as expected. Deletion of any of ugmA, ugeA, ugtA, their repression by alcA(p) or niiA(p), OR, ugmA overexpression by alcA(p), increased sensitivity to Caspofungin. Strains with alcA(p)-mediated overexpression of ugeA and ugtA had lower caspofungin sensitivity. Galf appears to play an important role in A. nidulans growth and vigor. |
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