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Functional Insights of MraZ on the Pathogenicity of Staphylococcus aureus
Bingjie Wang1, Jingjing Duan2, Ye Jin3
1Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China.
Introduction:
In recent years, multidrug-resistant methicillin-resistant Staphylococcus aureus has become increasingly prevalent, which raised a huge challenge to antibiotic treatment of infectious diseases. The anti-virulence strategy targeting virulent factors is a promising novel therapy for S. aureus infection. The virulence mechanism of S. aureus was needed to explore deeply to develop more targets and improve the effectiveness of anti-virulence strategies.
Results:
In this study, we found mraZ was highly conserved in S. aureus, and its production is homologous with the MraZ of Escherichia coli, a transcriptional regulator involved in the growth and cell division of E. coli. To investigate the function of mraZ in S. aureus, we constructed a MW2 mraZ deletion mutant and its complementary mutant for virulence comparison. Although no remarkable influence on the growth, the mraZ deletion mutant led to significantly reduced resistance to human neutrophils and decreased virulence in Galleria mellonella model as well as mouse skin and soft tissue infection models, indicating its essential contribution to virulence and immune evasion to support the pathogenicity of S. aureus infection. RNA-Seq and quantitative RT-qPCR revealed that MraZ is a multi-functional regulator; it involves in diverse biological processes and can up-regulate the expression of various virulence genes by agr and sarA.
Conclusion:
mraZ plays vital roles in the pathyogenicity of S. aureus via regulating many virulence genes. It may be an attractive target for anti-virulence therapy of S. aureus.
Insights
The gene mraZ is crucial for Staphylococcus aureus virulence and immune evasion. Deleting mraZ significantly reduces S. aureus pathogenicity, suggesting it as a potential target for anti-virulence therapies.
Area of Science:
- Microbiology
- Molecular Biology
- Pathogenesis
Background:
- Multidrug-resistant methicillin-resistant Staphylococcus aureus (MRSA) poses a significant threat to public health.
- Anti-virulence strategies offer a novel therapeutic approach by targeting bacterial virulence factors.
- Understanding S. aureus virulence mechanisms is essential for developing effective treatments.
Purpose of the Study:
- To investigate the role of the conserved gene mraZ in Staphylococcus aureus virulence.
- To explore mraZ as a potential target for anti-virulence therapies.
Main Methods:
- Construction and comparison of a mraZ deletion mutant and its complementary mutant in S. aureus MW2.
- Assessment of bacterial resistance to human neutrophils.
- Evaluation of virulence in Galleria mellonella and mouse skin and soft tissue infection models.
- Gene expression analysis using RNA-Sequencing (RNA-Seq) and quantitative reverse transcription PCR (RT-qPCR).
Main Results:
- The mraZ gene is highly conserved in S. aureus and its product is homologous to E. coli MraZ, a transcriptional regulator.
- MraZ deletion mutant showed no significant impact on bacterial growth but exhibited reduced resistance to human neutrophils.
- The mraZ deletion mutant displayed significantly decreased virulence in Galleria mellonella and mouse infection models.
- MraZ was identified as a multi-functional regulator that up-regulates the expression of various virulence genes, including those regulated by agr and sarA.
Conclusions:
- MraZ plays a critical role in Staphylococcus aureus pathogenicity by regulating multiple virulence genes.
- MraZ is a promising therapeutic target for developing novel anti-virulence strategies against S. aureus infections.