The following is a summary of “Purine Biosynthesis Repressor, PurR, Contributes to Vancomycin Susceptibility of Methicillin-resistant Staphylococcus aureus in Experimental Endocarditis,” published in the January 2024 issue of Infectious Diseases by Xiong et al.
Researchers conducted a retrospective study to address the significant morbidity and mortality associated with life-threatening endovascular infections, particularly infective endocarditis (IE), caused by Staphylococcus aureus, notably methicillin-resistant strains (MRSA), given the limited therapeutic alternatives available.
They examined the impact of the purine biosynthesis repressor, PurR, on the expression of virulence factors and the efficacy of vancomycin (VAN) treatment in experimental IE caused by MRSA.
The results showed that the PurR-mediated repression of purine biosynthesis was validated by the upregulation of purF expression and the production of an intermediate purine metabolite in the purR mutant strain. Heightened expression of the transcriptional regulators, sigB and sarA, along with their pivotal downstream virulence genes (e.g., fnbA and hla), was observed in the purR mutant both in vitro and within infected cardiac vegetations. PurR deficiency increased fnbA/fnbB transcription, resulting in greater fibronectin adhesion than the wild and purR-complemented strains. The PurR mutant resisted significantly reducing MRSA burden in target tissues following VAN treatment in the IE model.
Investigators concluded that purine pathway disruption in MRSA shows promise for novel antimicrobials targeting virulence and persistence in VAN treatment.
Source: academic.oup.com/jid/advance-article-abstract/doi/10.1093/infdis/jiad577/7595511
