Journal article
Systematic analysis of the Candida albicans kinome reveals environmentally contingent protein kinase-mediated regulation of filamentation and biofilm formation in vitro and in vivo
mBio, Vol.15(8), e0124924
07/01/2024
DOI: 10.1128/mbio.01249-24
PMCID: PMC11323567
PMID: 38949302
Abstract
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.
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.
Details
- Title: Subtitle
- Systematic analysis of the Candida albicans kinome reveals environmentally contingent protein kinase-mediated regulation of filamentation and biofilm formation in vitro and in vivo
- Creators
- Juraj Kramara - University of Iowa, Stead Family Department of PediatricsMin-Ju Kim - University of GeorgiaTomye L. Ollinger - University of Iowa, Stead Family Department of PediatricsLaura C. Ristow - University of IowaRohan S. Wakade - University of Iowa, Stead Family Department of PediatricsRobert Zarnowski - University of Wisconsin–MadisonMelanie Wellington - University of Iowa, Infectious Disease (Pediatrics)David R. Andes - University of Wisconsin–MadisonAaron G. Mitchell - University of GeorgiaDamian J. Krysan - University of Iowa, Infectious Disease (Pediatrics)
- Resource Type
- Journal article
- Publication Details
- mBio, Vol.15(8), e0124924
- DOI
- 10.1128/mbio.01249-24
- PMID
- 38949302
- PMCID
- PMC11323567
- ISSN
- 2150-7511
- eISSN
- 2150-7511
- Language
- English
- Electronic publication date
- 07/01/2024
- Academic Unit
- Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
- Record Identifier
- 9984650757902771
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