ArticleThe Journal of infectious diseases2020
The Stringent Response Contributes to Persistent Methicillin-Resistant Staphylococcus aureus Endovascular Infection Through the Purine Biosynthetic Pathway.
Article in The Journal of infectious diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- Article
- Antibiotic tolerance among clinical isolates: mechanisms, detection, prevalence, and significance.Clinical microbiology reviews · 2024Review
- Determinants of bacterial survival and proliferation in blood.FEMS microbiology reviews · 2024Review
- Bacterial heterogeneity and antibiotic persistence: bacterial mechanisms utilized in the host environment.Microbiology and molecular biology reviews : MMBR · 2023Review
- Gp05, a Prophage-Encoded Virulence Factor, Contributes to Persistent Methicillin-Resistant Staphylococcus aureus Endovascular Infection.Microbiology spectrum · 2023Article
- MRSA Isolates from Patients with Persistent Bacteremia Generate Nonstable Small Colony VariantsInfection and immunity · 2023Article
- Role of (p)ppGpp in antibiotic resistance, tolerance, persistence and survival in Firmicutes.microLife · 2023Review
- Molecular Characterization of Clinical Rel Mutations and Consequences for Resistance Expression and Fitness in Staphylococcus aureus.Antimicrobial agents and chemotherapy · 2022Article
- Antimicrobial Efficacy against Antibiotic-TolerantAntibiotics (Basel, Switzerland) · 2022Article
- Identification of Methicillin-ResistantAntibiotics (Basel, Switzerland) · 2022Article
- Proteoglycan 4 (lubricin) is a highly sialylated glycoprotein associated with cardiac valve damage in animal models of infective endocarditis.Glycobiology · 2021Article
- Phenol-soluble modulins α are major virulence factors ofVirulence · 2021Article
- Coagulase-negative staphylococci release a purine analog that inhibits Staphylococcus aureus virulence.Nature communications · 2021Article
- Inducible expression of (pp)pGpp synthetases in Staphylococcus aureus is associated with activation of stress response genes.PLoS genetics · 2020Article
- Distinct Effectiveness of Oritavancin against Tolerance-InducedAntibiotics (Basel, Switzerland) · 2020Article
- Survival of the Fittest: The Relationship of (p)ppGpp With Bacterial Virulence.Frontiers in microbiology · 2020Review
- Pleiotropic Effects of Bacterial Small Alarmone Synthetases: Underscoring the Dual-Domain Small Alarmone Synthetases inFrontiers in microbiology · 2020Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Persistent methicillin-resistant Staphylococcus aureus (MRSA) endovascular infections represent a significant clinical-therapeutic challenge. Of particular concern is antibiotic treatment failure in infections caused by MRSA that are "susceptible" to antibiotic in vitro. In the current study, we investigate specific purine biosynthetic pathways and stringent response mechanism(s) related to this life-threatening syndrome using genetic matched persistent and resolving MRSA clinical bacteremia isolates (PB and RB, respectively), and isogenic MRSA strain sets. We demonstrate that PB isolates (vs RB isolates) have significantly higher (p)ppGpp production, phenol-soluble-modulin expression, polymorphonuclear leukocyte lysis and survival, fibronectin/endothelial cell (EC) adherence, and EC damage. Importantly, an isogenic strain set, including JE2 parental, relP-mutant and relP-complemented strains, translated the above findings into significant outcome differences in an experimental endocarditis model. These observations indicate a significant regulation of purine biosynthesis on stringent response, and suggest the existence of a previously unknown adaptive genetic mechanism in persistent MRSA infection.
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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.