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Updated: Jan 23, 2026
Genotyping of Staphylococcus aureus by Ribosomal Spacer PCR RS-PCR
Published on: November 4, 2016
The purine biosynthesis regulator PurR moonlights as a virulence regulator in Staphylococcus aureus
William E Sause1, Divya Balasubramanian1, Irnov Irnov1
1Department of Microbiology, New York University School of Medicine, New York, NY 10016.
Abstract:
The pathogen Staphylococcus aureus colonizes and infects a variety of different sites within the human body. To adapt to these different environments, S. aureus relies on a complex and finely tuned regulatory network. While some of these networks have been well-elucidated, the functions of more than 50% of the transcriptional regulators in S. aureus remain unexplored. Here, we assess the contribution of the LacI family of metabolic regulators to staphylococcal virulence. We found that inactivating the purine biosynthesis regulator purR resulted in a strain that was acutely virulent in bloodstream infection models in mice and in ex vivo models using primary human neutrophils. Remarkably, these enhanced pathogenic traits are independent of purine biosynthesis, as the purR mutant was still highly virulent in the presence of mutations that disrupt PurR's canonical role. Through the use of transcriptomics coupled with proteomics, we revealed that a number of virulence factors are differentially regulated in the absence of purR Indeed, we demonstrate that PurR directly binds to the promoters of genes encoding virulence factors and to master regulators of virulence. These results guided us into further ex vivo and in vivo studies, where we discovered that S. aureus toxins drive the death of human phagocytes and mice, whereas the surface adhesin FnbA contributes to the increased bacterial burden observed in the purR mutant. Thus, S. aureus repurposes a metabolic regulator to directly control the expression of virulence factors, and by doing so, tempers its pathogenesis.
Insights
The purine regulator PurR in Staphylococcus aureus controls virulence independently of its known function. Deleting purR enhances bacterial toxins and adhesins, increasing disease severity.
Area of Science:
- Microbiology
- Molecular Biology
- Pathogenesis
Background:
- Staphylococcus aureus utilizes complex regulatory networks for adaptation and infection.
- Many transcriptional regulators in S. aureus, including metabolic regulators, have unexplored functions.
- Understanding these regulators is crucial for deciphering staphylococcal virulence.
Purpose of the Study:
- To investigate the role of the LacI family of metabolic regulators in Staphylococcus aureus virulence.
- To determine the contribution of the purine biosynthesis regulator PurR to staphylococcal pathogenesis.
- To elucidate the mechanisms by which PurR influences virulence factor expression.
Main Methods:
- Genetic inactivation of the purR gene in Staphylococcus aureus.
- Assessment of bacterial virulence in murine bloodstream infection models.
- Evaluation of virulence in ex vivo models using primary human neutrophils.
- Transcriptomic and proteomic analyses to identify differentially regulated genes and proteins.
- Electrophoretic mobility shift assays to confirm direct binding of PurR to target gene promoters.
Main Results:
- Inactivation of purR resulted in hypervirulence in mouse models and human neutrophil infections.
- Enhanced virulence was observed even when PurR's canonical purine biosynthesis role was disrupted.
- Transcriptomics and proteomics revealed differential regulation of numerous virulence factors in the purR mutant.
- PurR was shown to directly bind to the promoters of virulence factor genes and master virulence regulators.
- Staphylococcus aureus toxins were identified as key drivers of host cell death, and FnbA contributed to bacterial burden.
Conclusions:
- Staphylococcus aureus repurposes the metabolic regulator PurR to directly control virulence factor expression.
- PurR acts as a repressor of virulence, tempering pathogenesis when functional.
- Targeting PurR or its regulatory network presents a potential strategy for combating S. aureus infections.
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