ArticleThe Journal of infectious diseases2024
The Purine Biosynthesis Repressor, PurR, Contributes to Vancomycin Susceptibility of Methicillin-resistant Staphylococcus aureus in Experimental Endocarditis.
Article in The Journal of infectious diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 12 citations in OpenAlex.
- Heterogeneity in microbial antibiotic responses: genetic basis and within-host evolution.Trends in genetics : TIG · 2026Review
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- Global response to antibiotic exposure reveals a critical role for nucleotide metabolism in high-level β-lactam tolerance.npj antimicrobials and resistance · 2026Article
- Global response to antibiotic exposure uncovers a critical role for nucleotide metabolism in high-level β-lactam tolerance.Research square · 2025Article
- Recent advances in metabolic engineering of Escherichia coli for riboflavin biosynthesis.World journal of microbiology & biotechnology · 2025Review
- Staphylococcus aureus COL: An Atypical Model Strain of MRSA That Exhibits Slow Growth and Antibiotic Tolerance due to a Mutation in PRPP Synthetase.Molecular microbiology · 2025Article
- Pathoadapative Genomic Determinants ofMicroorganisms · 2025Article
- The impact of bacterial purine metabolism on antibiotic efficacy.npj antimicrobials and resistance · 2025Review
- Review
- Simulated exposures of oritavancin in in vitro pharmacodynamic models select for methicillin-resistant Staphylococcus aureus with reduced susceptibility to oritavancin but minimal cross-resistance or seesaw effect with other antimicrobials.The Journal of antimicrobial chemotherapy · 2025Article
- Antibiotic tolerance among clinical isolates: mechanisms, detection, prevalence, and significance.Clinical microbiology reviews · 2024Review
- Clinical and in vitro models identify distinct adaptations enhancing Staphylococcus aureus pathogenesis in human macrophages.PLoS pathogens · 2024Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundStaphylococcus aureus is the most common cause of life-threatening endovascular infections, including infective endocarditis (IE). These infections, especially when caused by methicillin-resistant strains (MRSA), feature limited therapeutic options and high morbidity and mortality rates.
methodsHerein, we investigated the role of the purine biosynthesis repressor, PurR, in virulence factor expression and vancomycin (VAN) treatment outcomes in experimental IE due to MRSA.
resultsThe PurR-mediated repression of purine biosynthesis was confirmed by enhanced purF expression and production of an intermediate purine metabolite in purR mutant strain. In addition, enhanced expression of the transcriptional regulators, sigB and sarA, and their key downstream virulence genes (eg, fnbA, and hla) was demonstrated in the purR mutant in vitro and within infected cardiac vegetations. Furthermore, purR deficiency enhanced fnbA/fnbB transcription, translating to increased fibronectin adhesion versus the wild type and purR-complemented strains. Notably, the purR mutant was refractory to significant reduction in target tissues MRSA burden following VAN treatment in the IE model.
conclusionsThese findings suggest that the purine biosynthetic pathway intersects the coordination of virulence factor expression and in vivo persistence during VAN treatment, and may represent an avenue for novel antimicrobial development targeting MRSA.
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