دورية أكاديمية
أعرض في EDS

Imaging-Based Screening Identifies Modulators of the eIF3 Translation Initiation Factor Complex in Candida albicans.

التفاصيل البيبلوغرافية
العنوان: Imaging-Based Screening Identifies Modulators of the eIF3 Translation Initiation Factor Complex in Candida albicans.
المؤلفون: Metzner K; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA., O'Meara MJ; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA., Halligan B; University of Michigan Center for Drug Repurposing, Ann Arbor, Michigan, USA.; Department of Internal Medicine, Gastroenterology, University of Michigan Medical School, Ann Arbor, Michigan, USA., Wotring JW; University of Michigan Center for Drug Repurposing, Ann Arbor, Michigan, USA.; Department of Medicinal Chemistry, College of Pharmacy, Ann Arbor, Michigan, USA., Sexton JZ; University of Michigan Center for Drug Repurposing, Ann Arbor, Michigan, USA.; Department of Internal Medicine, Gastroenterology, University of Michigan Medical School, Ann Arbor, Michigan, USA.; Department of Medicinal Chemistry, College of Pharmacy, Ann Arbor, Michigan, USA., O'Meara TR; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
المصدر: Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2023 Jul 18; Vol. 67 (7), pp. e0050323. Date of Electronic Publication: 2023 Jun 29.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 0315061 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-6596 (Electronic) Linking ISSN: 00664804 NLM ISO Abbreviation: Antimicrob Agents Chemother Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, American Society for Microbiology
مواضيع طبية MeSH: Candida albicans*/metabolism , Antifungal Agents*/therapeutic use, Animals ; Humans ; Fungal Proteins/genetics ; Fungal Proteins/metabolism ; Virulence Factors/metabolism ; Peptide Initiation Factors/metabolism ; Hyphae ; Mammals/metabolism
مستخلص: Fungal pathogens like Candida albicans can cause devastating human disease. Treatment of candidemia is complicated by the high rate of resistance to common antifungal therapies. Additionally, there is host toxicity associated with many antifungal compounds due to the conservation between essential mammalian and fungal proteins. An attractive new approach for antimicrobial development is to target virulence factors: non-essential processes that are required for the organism to cause disease in human hosts. This approach expands the potential target space while reducing the selective pressure toward resistance, as these targets are not essential for viability. In C. albicans, a key virulence factor is the ability to transition to hyphal morphology. We developed a high-throughput image analysis pipeline to distinguish between yeast and filamentous growth in C. albicans at the single cell level. Based on this phenotypic assay, we screened the FDA drug repurposing library of 2,017 compounds for their ability to inhibit filamentation and identified 33 compounds that block the hyphal transition in C. albicans with IC 50 values ranging from 0.2 to 150 μM. Multiple compounds showed a phenyl sulfone chemotype, prompting further analysis. Of these phenyl sulfones, NSC 697923 displayed the most efficacy, and by selecting for resistant mutants, we identified eIF3 as the target of NSC 697923 in C. albicans.
التعليقات: Update of: bioRxiv. 2023 Apr 19;:. (PMID: 37131825)
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معلومات مُعتمدة: K22 AI137299 United States AI NIAID NIH HHS; UL1 TR002240 United States TR NCATS NIH HHS; UM1 TR004404 United States TR NCATS NIH HHS
فهرسة مساهمة: Keywords: Candida albicans; antifungal agents; morphological profiling
المشرفين على المادة: 0 (Antifungal Agents)
0 (Fungal Proteins)
0 (Virulence Factors)
0 (Peptide Initiation Factors)
تواريخ الأحداث: Date Created: 20230629 Date Completed: 20230717 Latest Revision: 20240216
رمز التحديث: 20240216
مُعرف محوري في PubMed: PMC10353439
DOI: 10.1128/aac.00503-23
PMID: 37382550
قاعدة البيانات: MEDLINE
الوصف
تدمد:1098-6596
DOI:10.1128/aac.00503-23