ArticleJournal of bacteriology2010
CcpA mediates proline auxotrophy and is required for Staphylococcus aureus pathogenesis.
Article in Journal of bacteriology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 83 citations in OpenAlex.
- Article
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- Glucose-induced active lysogeny of prophage ΦSa3XN promotes Staphylococcus aureus virulence.Virology journal · 2025Article
- Assessment of the biofilm formation capacities of Staphylococcus aureus strains Newman and Newman D2C in vitro and in vivo.Scientific reports · 2025Article
- New insights into the cultivability of human milk bacteria from ingestion to digestion and implications for their Immunomodulatory properties.Scientific reports · 2025Article
- Regulatory dynamics of arginine metabolism in Staphylococcus aureus.Biochemical Society transactions · 2024Review
- Staphylococcus aureus adapts to exploit collagen-derived proline during chronic infection.Nature microbiology · 2024Article
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- GlutamateJournal of bacteriology · 2024Article
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- Targeting and arginine-driven synergizing photodynamic therapy with nutritional immunotherapy nanosystems for combating MRSA biofilms.Science advances · 2023Article
- Proline transporters ProT and PutP are required for Staphylococcus aureus infection.PLoS pathogens · 2023Article
- Characterization of the Secreted Acid Phosphatase SapS Reveals a Novel Virulence Factor ofInternational journal of molecular sciences · 2022Article
- Article
- Methods for Quantifying the Metabolic Boundary Fluxes of Cell Cultures in Large Cohorts by High-Resolution Hydrophilic Liquid Chromatography Mass Spectrometry.Analytical chemistry · 2022Article
- Staphylococcus aureus Does Not Synthesize Arginine from Proline under Physiological Conditions.Journal of bacteriology · 2022Article
- StaphylococcalInternational journal of molecular sciences · 2022Article
- Adaptive Metabolism ofJournal of proteome research · 2022Article
- Genome-Scale Metabolic Modelling Approach to Understand the Metabolism of the Opportunistic Human PathogenMetabolites · 2022Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Human clinical isolates of Staphylococcus aureus, for example, strains Newman and N315, cannot grow in the absence of proline, albeit their sequenced genomes harbor genes for two redundant proline synthesis pathways. We show here that under selective pressure, S. aureus Newman generates proline-prototrophic variants at a frequency of 3 x 10(-6), introducing frameshift and missense mutations in ccpA or IS1811 insertions in ptsH, two regulatory genes that carry out carbon catabolite repression (CCR) in staphylococci and other Gram-positive bacteria. S. aureus Newman variants with mutations in rocF (arginase), rocD (ornithine aminotransferase), and proC (Delta(1)-pyrroline 5-carboxylate [P5C] reductase) are unable to generate proline-prototrophic variants, whereas a variant with a mutation in ocd (ornithine cyclodeaminase) is unaffected. Transposon insertion in ccpA also restored proline prototrophy. CcpA was shown to repress transcription of rocF and rocD, encoding the first two enzymes, but not of proC, encoding the third and final enzyme in the P5C reductase pathway. CcpA bound to the upstream regions of rocF and rocD but not to that of proC. CcpA's binding to the upstream regions was greatly enhanced by phosphorylated HPr. The CCR-mediated proline auxotrophy was lifted when nonpreferred carbohydrates were used as the sole carbon source. The ccpA mutant displayed reduced staphylococcal load and replication in a murine model of staphylococcal abscess formation, indicating that carbon catabolite repression presents an important pathogenesis strategy of S. aureus infections.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.