期刊
MICROORGANISMS
卷 9, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/microorganisms9102148
关键词
metabolism; flux balance analysis; phosphorylation; regulation; riboswitch; PknB; Stp; yvcK/glmR operon & nbsp;& nbsp;
类别
资金
- DFG [GRK 2157, 270563345]
- Land Bavaria [TR221]
- DFG [324392634]
The serine/threonine kinase PknB and its corresponding phosphatase Stp play important roles in regulating various cell functions in the pathogen S. aureus. They impact amino acid catabolism, gluconeogenesis, and synthesis of key cellular components. The study also highlighted interactions of PknB with CdaA and the yvcK/glmR regulon, as well as the phosphorylation-mediated decrease in expression of virulence factors in S. aureus.
Serine/threonine kinase PknB and its corresponding phosphatase Stp are important regulators of many cell functions in the pathogen S. aureus. Genome-scale gene expression data of S. aureus strain NewHG (sigB(+)) elucidated their effect on physiological functions. Moreover, metabolic modelling from these data inferred metabolic adaptations. We compared wild-type to deletion strains lacking pknB, stp or both. Ser/Thr phosphorylation of target proteins by PknB switched amino acid catabolism off and gluconeogenesis on to provide the cell with sufficient components. We revealed a significant impact of PknB and Stp on peptidoglycan, nucleotide and aromatic amino acid synthesis, as well as catabolism involving aspartate transaminase. Moreover, pyrimidine synthesis was dramatically impaired by stp deletion but only slightly by functional loss of PknB. In double knockouts, higher activity concerned genes involved in peptidoglycan, purine and aromatic amino acid synthesis from glucose but lower activity of pyrimidine synthesis from glucose compared to the wild type. A second transcriptome dataset from S. aureus NCTC 8325 (sigB(-)) validated the predictions. For this metabolic adaptation, PknB was found to interact with CdaA and the yvcK/glmR regulon. The involved GlmR structure and the GlmS riboswitch were modelled. Furthermore, PknB phosphorylation lowered the expression of many virulence factors, and the study shed light on S. aureus infection processes.
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