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Systematic analysis of the Candida albicans kinome reveals environmentally contingent protein kinase-mediated regulation of filamentation and biofilm formation in vitro and in vivo .

التفاصيل البيبلوغرافية
العنوان: Systematic analysis of the Candida albicans kinome reveals environmentally contingent protein kinase-mediated regulation of filamentation and biofilm formation in vitro and in vivo .
المؤلفون: Kramara J; Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA., Kim M-J; Department of Microbiology, University of Georgia, Athens, Georgia, USA., Ollinger TL; Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA., Ristow LC; Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA., Wakade RS; Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA., Zarnowski R; Department of Medicine, Section of Infectious Disease, University of Wisconsin, Madison, Wisconsin, USA.; Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, Wisconsin, USA., Wellington M; Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA., Andes DR; Department of Medicine, Section of Infectious Disease, University of Wisconsin, Madison, Wisconsin, USA.; Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, Wisconsin, USA., Mitchell AG; Department of Microbiology, University of Georgia, Athens, Georgia, USA., Krysan DJ; Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.; Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
المصدر: MBio [mBio] 2024 Aug 14; Vol. 15 (8), pp. e0124924. Date of Electronic Publication: 2024 Jul 01.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Society for Microbiology
مواضيع طبية MeSH: Candida albicans*/genetics , Candida albicans*/enzymology , Candida albicans*/pathogenicity , Candida albicans*/physiology , Biofilms*/growth & development , Protein Kinases*/genetics , Protein Kinases*/metabolism, Virulence ; Animals ; Fungal Proteins/genetics ; Fungal Proteins/metabolism ; Candidiasis/microbiology ; Gene Expression Regulation, Fungal ; Mice ; Hyphae/growth & development ; Hyphae/genetics
مستخلص: Protein kinases are critical regulatory proteins in both prokaryotes and eukaryotes. Accordingly, protein kinases represent a common drug target for a wide range of human diseases. Therefore, understanding protein kinase function in human pathogens such as the fungus Candida albicans is likely to extend our knowledge of its pathobiology and identify new potential therapies. To facilitate the study of C. albicans protein kinases, we constructed a library of 99 non-essential protein kinase homozygous deletion mutants marked with barcodes in the widely used SN genetic background. Here, we describe the construction of this library and the characterization of the competitive fitness of the protein kinase mutants under 11 different growth and stress conditions. We also screened the library for protein kinase mutants with altered filamentation and biofilm formation, two critical virulence traits of C. albicans . An extensive network of protein kinases governs these virulence traits in a manner highly dependent on the specific environmental conditions. Studies on specific protein kinases revealed that (i) the cell wall integrity MAPK pathway plays a condition-dependent role in filament initiation and elongation; (ii) the hyper-osmolar glycerol MAPK pathway is required for both filamentation and biofilm formation, particularly in the setting of in vivo catheter infection; and (iii) Sok1 is dispensable for filamentation in hypoxic environments at the basal level of a biofilm but is required for filamentation in normoxia. In addition to providing a new genetic resource for the community, these observations emphasize the environmentally contingent function of C. albicans protein kinases.IMPORTANCE Candida albicans is one of the most common causes of fungal disease in humans for which new therapies are needed. Protein kinases are key regulatory proteins and are increasingly targeted by drugs for the treatment of a wide range of diseases. Understanding protein kinase function in C. albicans pathogenesis may facilitate the development of new antifungal drugs. Here, we describe a new library of 99 protein kinase deletion mutants to facilitate the study of protein kinases. Furthermore, we show that the function of protein kinases in two virulence-related processes, filamentation and biofilm formation, is dependent on the specific environmental conditions.
Competing Interests: The authors declare no conflict of interest.
التعليقات: Comment in: mBio. 2024 Aug 14;15(8):e0169824. doi: 10.1128/mbio.01698-24. (PMID: 39058031)
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معلومات مُعتمدة: R21AI157341 HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID); R01AI133409 HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
فهرسة مساهمة: Keywords: Candida albicans; biofilm; filamentation; protein kinase
المشرفين على المادة: EC 2.7.- (Protein Kinases)
0 (Fungal Proteins)
تواريخ الأحداث: Date Created: 20240701 Date Completed: 20240814 Latest Revision: 20240815
رمز التحديث: 20240815
DOI: 10.1128/mbio.01249-24
PMID: 38949302
قاعدة البيانات: MEDLINE
الوصف
تدمد:2150-7511
DOI:10.1128/mbio.01249-24