ArticleThe Journal of biological chemistry2012
A novel mode of regulation of the Staphylococcus aureus catabolite control protein A (CcpA) mediated by Stk1 protein phosphorylation.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 68 citations in OpenAlex.
- Stk1 is required for BlaR1-mediated broad-spectrum β-lactam resistance in epidemic-causing strains of Staphylococcus aureus.Nature communications · 2026Article
- Structure-Based Strategy Reveals a Novel Ligand Binding Site inACS omega · 2026Article
- CcpA promotesmLife · 2025Article
- Loratadine Combats Methicillin-ResistantACS infectious diseases · 2024Article
- Insights into Kinases of ESKAPE Pathogens for Therapeutic Interventions.Cardiovascular & hematological agents in medicinal chemistry · 2024Review
- Article
- StkP- and PhpP-Mediated Posttranslational Modifications Modulate the S. pneumoniae Metabolism, Polysaccharide Capsule, and Virulence.Infection and immunity · 2023Article
- Phosphorylation of GntR reduces Streptococcus suis oxidative stress resistance and virulence by inhibiting NADH oxidase transcription.PLoS pathogens · 2023Article
- Identification of serine/threonine kinases that regulate metabolism and sporulation in Clostridium beijerinckii.Applied microbiology and biotechnology · 2022Article
- CcpA RegulatesAntibiotics (Basel, Switzerland) · 2022Article
- The RNA-bound proteome of MRSA reveals post-transcriptional roles for helix-turn-helix DNA-binding and Rossmann-fold proteins.Nature communications · 2022Article
- Article
- The Low-Molecular Weight Protein Arginine Phosphatase PtpB Affects Nuclease Production, Cell Wall Integrity, and Uptake Rates ofInternational journal of molecular sciences · 2021Article
- Staphylococcal Infections: Host and Pathogenic Factors.Microorganisms · 2021Article
- The enterococcal PASTA kinase: A sentinel for cell envelope stress.Molecular oral microbiology · 2021Review
- Impact of the Histidine-Containing Phosphocarrier Protein HPr on Carbon Metabolism and Virulence inMicroorganisms · 2021Article
- Revealing 29 sets of independently modulated genes inProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Metabolic control of virulence factor production in Staphylococcus aureus.Current opinion in microbiology · 2020Review
- Defeating Antibiotic-Resistant Bacteria: Exploring Alternative Therapies for a Post-Antibiotic Era.International journal of molecular sciences · 2020Review
- An integrated computational and experimental study to investigate Staphylococcus aureus metabolism.NPJ systems biology and applications · 2020Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Staphylococcus aureus serine/threonine protein kinase Stk1 (also known as PknB) affects different key pathways such as cell wall metabolism, antibiotic susceptibility, and regulation of virulence. Here we report that the catabolite control protein A (CcpA), a highly conserved regulator of carbon catabolite repression and virulence in a number of gram-positive pathogens, was efficiently phosphorylated in vitro and in vivo by Stk1 in S. aureus, whereas the CcpA homologues of Bacillus subtilis and Bacillus anthracis were not affected by the Stk1 orthologue PrkC. Mass spectrometry and mutational analyses identified Thr-18 and Thr-33 as the phosphoacceptors; both are located in the DNA binding domain of this protein. Electrophoretic mobility shift assays demonstrated that the CcpA DNA binding activity was completely abrogated for the phosphorylated CcpA. The physiological relevance of CcpA phosphorylation was assessed by generating CcpA phosphoablative (T18A/T33A) or phosphomimetic (T18D/T33D) mutants. In contrast to the wild-type and phosphoablative ccpA alleles, introduction of the phosphomimetic ccpA allele in a ΔccpA mutant failed to restore the parental biofilm formation profile and the transcription of citZ and hla to levels seen with the wild type. The strong up regulation of ccpA transcripts and CcpA level in the ccpA mutant trans-complemented with the phosphomimetic CcpA variant suggest furthermore that CcpA acts as a negative regulator of its own expression. Together, these findings demonstrate that Stk1-driven phosphorylation of CcpA inhibits its DNA binding activity toward its regulon in S. aureus, representing a novel regulatory mechanism of CcpA activity in addition to the well known regulation via HprKP/Hpr in this clinically important pathogen.
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