24845
2021
eng
10
9
article
1
--
2021-10-14
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Staphylococcus aureus transcriptome data and metabolic modelling investigate the interplay of Ser/Thr kinase PknB, its phosphatase Stp, the glmR/yvcK regulon and the cdaA operon for metabolic adaptation
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.
Microorganisms
2076-2607
10.3390/microorganisms9102148
urn:nbn:de:bvb:20-opus-248459
2021-11-04T22:01:40+00:00
sword
swordwue
attachment; filename=deposit.zip
d0f205c6e2298529a2ec770e1a0e1ce0
Microorganisms (2021) 9:10, 2148. https://doi.org/10.3390/microorganisms9102148
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Chunguang Liang
Ana B. Rios-Miguel
Marcel Jarick
Priya Neurgaonkar
Myriam Girard
Patrice François
Jacques Schrenzel
Eslam S. Ibrahim
Knut Ohlsen
Thomas Dandekar
eng
uncontrolled
metabolism
eng
uncontrolled
flux balance analysis
eng
uncontrolled
phosphorylation
eng
uncontrolled
regulation
eng
uncontrolled
riboswitch
eng
uncontrolled
PknB
eng
uncontrolled
Stp
eng
uncontrolled
yvcK/glmR operon
Biowissenschaften; Biologie
open_access
Institut für Molekulare Infektionsbiologie
Theodor-Boveri-Institut für Biowissenschaften
Import
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/24845/microorganisms-09-02148-v2.pdf
17733
2018
eng
13693
8
article
1
2019-02-26
--
--
The serine/threonine kinase Stk and the phosphatase Stp regulate cell wall synthesis in Staphylococcus aureus
The cell wall synthesis pathway producing peptidoglycan is a highly coordinated and tightly regulated process. Although the major components of bacterial cell walls have been known for decades, the complex regulatory network controlling peptidoglycan synthesis and many details of the cell division machinery are not well understood. The eukaryotic-like serine/threonine kinase Stk and the cognate phosphatase Stp play an important role in cell wall biosynthesis and drug resistance in S. aureus. We show that stp deletion has a pronounced impact on cell wall synthesis. Deletion of stp leads to a thicker cell wall and decreases susceptibility to lysostaphin. Stationary phase Δstp cells accumulate peptidoglycan precursors and incorporate higher amounts of incomplete muropeptides with non-glycine, monoglycine and monoalanine interpeptide bridges into the cell wall. In line with this cell wall phenotype, we demonstrate that the lipid II:glycine glycyltransferase FemX can be phosphorylated by the Ser/Thr kinase Stk in vitro. Mass spectrometric analyses identify Thr32, Thr36 and Ser415 as phosphoacceptors. The cognate phosphatase Stp dephosphorylates these phosphorylation sites. Moreover, Stk interacts with FemA and FemB, but is unable to phosphorylate them. Our data indicate that Stk and Stp modulate cell wall synthesis and cell division at several levels.
Scientific Reports
10.1038/s41598-018-32109-7
urn:nbn:de:bvb:20-opus-177333
Scientific Reports (2018) 8:13693. DOI: 10.1038/s41598-018-32109-7
ESF_14-BM-A55-0005_16
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Marcel Jarick
Ute Bertsche
Mark Stahl
Daniel Schultz
Karen Methling
Michael Lalk
Christian Stigloher
Mirco Steger
Andreas Schlosser
Knut Ohlsen
eng
uncontrolled
bacterial transcription
eng
uncontrolled
pathogens
eng
uncontrolled
cell wall synthesis
Biowissenschaften; Biologie
open_access
Institut für Molekulare Infektionsbiologie
Theodor-Boveri-Institut für Biowissenschaften
OpenAIRE
Förderzeitraum 2018
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/17733/Jarick_Scientific_Reports.pdf