A tyrosine phosphoregulatory system controls exopolysaccharide biosynthesis and biofilm formation in Vibrio cholerae

Autor: Jacqueline Osorio, Fitnat H. Yildiz, Monique E. Porcella, Seth M. Rubin, Sarvind Tripathi, Kyle A. Floyd, Carmen Schwechheimer, Elise R. Brown, Praveen K. Singh, Knut Drescher, Joseph T. M. Kiblen, Kassidy Hebert, Fernando A. Pagliai
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Protein tyrosine phosphatase
Pathology and Laboratory Medicine
medicine.disease_cause
Biochemistry
Tyrosine Kinases
chemistry.chemical_compound
Aromatic Amino Acids
Medicine and Health Sciences
Post-Translational Modification
Phosphorylation
Amino Acids
Tyrosine
Biology (General)
0303 health sciences
Organic Compounds
Chemistry
Polysaccharides
Bacterial
Biofilm matrix
Bacterial Pathogens
Enzymes
Cell biology
Medical Microbiology
Vibrio cholerae
Physical Sciences
Pathogens
Tyrosine kinase
Research Article
QH301-705.5
Immunology
macromolecular substances
Biosynthesis
Microbiology
03 medical and health sciences
Bacterial Proteins
Hydroxyl Amino Acids
Virology
Vibrio Cholerae
Genetics
medicine
Microbial Pathogens
Molecular Biology
Vibrio
030304 developmental biology
Bacteria
030306 microbiology
Organic Chemistry
Chemical Compounds
Organisms
Phosphatases
Biofilm
Biology and Life Sciences
Proteins
Bacteriology
Tyrosine phosphorylation
RC581-607
Biofilms
Enzymology
Parasitology
Protein Multimerization
Protein Tyrosine Phosphatases
Immunologic diseases. Allergy
Bacterial Biofilms
Protein Kinases
Zdroj: PLoS Pathogens, Vol 16, Iss 8, p e1008745 (2020)
PLOS Pathogens
PLoS Pathogens
ISSN: 1553-7374
1553-7366
Popis: Production of an extracellular matrix is essential for biofilm formation, as this matrix both secures and protects the cells it encases. Mechanisms underlying production and assembly of matrices are poorly understood. Vibrio cholerae, relies heavily on biofilm formation for survival, infectivity, and transmission. Biofilm formation requires Vibrio polysaccharide (VPS), which is produced by vps gene-products, yet the function of these products remains unknown. Here, we demonstrate that the vps gene-products vpsO and vpsU encode respectively for a tyrosine kinase and a cognate tyrosine phosphatase. Collectively, VpsO and VpsU act as a tyrosine phosphoregulatory system to modulate VPS production. We present structures of VpsU and the kinase domain of VpsO, and we report observed autocatalytic tyrosine phosphorylation of the VpsO C-terminal tail. The position and amount of tyrosine phosphorylation in the VpsO C-terminal tail represses VPS production and biofilm formation through a mechanism involving the modulation of VpsO oligomerization. We found that tyrosine phosphorylation enhances stability of VpsO. Regulation of VpsO phosphorylation by the phosphatase VpsU is vital for maintaining native VPS levels. This study provides new insights into the mechanism and regulation of VPS production and establishes general principles of biofilm matrix production and its inhibition.
Author summary The biofilm life style protects microbes from a plethora of harm, to increase their survival and pathogenicity. Exopolysaccharides are the essential glue of the microbial biofilm matrix, and loss of this glue negates biofilm formation and renders cells more sensitive to antimicrobial agents. Here, we show that a tyrosine phosphoregulatory system controls the biosynthesis and abundance of Vibrio exopolysaccharide (VPS), an essential biofilm component of the pathogen Vibrio cholerae. The phosphorylation state of the tyrosine autokinase VpsO, mediated by the tyrosine phosphatase VpsU, directly modulates VPS production and also affects the kinase’s own degradation, to regulate VPS production. This study provides new insights into the mechanisms of V. cholerae biofilm formation and consequently ways to combat pathogens more broadly, due to conservation of tyrosine phosphoregulatory systems among exopolysaccharide producing bacteria.
Databáze: OpenAIRE
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