ArticlePLoS pathogens2012
CcpA regulates arginine biosynthesis in Staphylococcus aureus through repression of proline catabolism.
Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 113 citations in OpenAlex.
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- Bacterial metabolic remodeling by convergent evolution unlocks nutrient availability after a host switch.Science advances · 2026Article
- ArgT functions as an arginine transporter inJournal of bacteriology · 2025Article
- CcpA promotesmLife · 2025Article
- Growth and acetate metabolism ofApplied and environmental microbiology · 2025Article
- The Multitarget Compound ZLY032 Achieves Treatment of Chronic Wounds.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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- Genome-scale metabolic model ofmSystems · 2025Article
- Transcriptional profiling reveals the effect of arginine on Actinobacillus succinogenes growth and fermentation.World journal of microbiology & biotechnology · 2025Article
- Regulatory dynamics of arginine metabolism in Staphylococcus aureus.Biochemical Society transactions · 2024Review
- Restriction of arginine induces antibiotic tolerance in Staphylococcus aureus.Nature communications · 2024Article
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- GlutamateJournal of bacteriology · 2024Article
- Genome-wide transcription response ofFrontiers in microbiology · 2024Article
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- Secretory IgA impacts the microbiota density in the human nose.Microbiome · 2023Article
- Metabolic reprogramming and altered cell envelope characteristics in a pentose phosphate pathway mutant increases MRSA resistance to β-lactam antibiotics.PLoS pathogens · 2023Article
- Group B Streptococcus Cas9 variants provide insight into programmable gene repression and CRISPR-Cas transcriptional effects.Communications biology · 2023Article
- Hyperglycemia Increases Severity of Staphylococcus aureus Osteomyelitis and Influences Bacterial Genes Required for Survival in Bone.Infection and immunity · 2023Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Staphylococcus aureus is a leading cause of community-associated and nosocomial infections. Imperative to the success of S. aureus is the ability to adapt and utilize nutrients that are readily available. Genomic sequencing suggests that S. aureus has the genes required for synthesis of all twenty amino acids. However, in vitro experimentation demonstrates that staphylococci have multiple amino acid auxotrophies, including arginine. Although S. aureus possesses the highly conserved anabolic pathway that synthesizes arginine via glutamate, we demonstrate here that inactivation of ccpA facilitates the synthesis of arginine via the urea cycle utilizing proline as a substrate. Mutations within putA, rocD, arcB1, argG and argH abolished the ability of S. aureus JE2 ccpA::tetL to grow in the absence of arginine, whereas an interruption in argJBCF, arcB2, or proC had no effect. Furthermore, nuclear magnetic resonance demonstrated that JE2 ccpA::ermB produced (13)C(5) labeled arginine when grown with (13)C(5) proline. Taken together, these data support the conclusion that S. aureus synthesizes arginine from proline during growth on secondary carbon sources. Furthermore, although highly conserved in all sequenced S. aureus genomes, the arginine anabolic pathway (ArgJBCDFGH) is not functional under in vitro growth conditions. Finally, a mutation in argH attenuated virulence in a mouse kidney abscess model in comparison to wild type JE2 demonstrating the importance of arginine biosynthesis in vivo via the urea cycle. However, mutations in argB, argF, and putA did not attenuate virulence suggesting both the glutamate and proline pathways are active and they, or their pathway intermediates, can complement each other in vivo.
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Registered trials
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.