Related Experiment Video
Updated: Jun 14, 2025
Development and Assessment of Intracellular Infection Models for Staphylococcus aureus
Published on: January 17, 2025
YjbH contributes to Staphylococcus aureus skin pathology and immune response through Agr-mediated α-toxin regulation
Aubrey K G McReynolds1, Emma A Pagella1, Miranda J Ridder1
1Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS, USA.
Abstract:
Staphylococcus aureus is the most common cause of skin and soft tissue infections (SSTIs) with Methicillin-Resistant S. aureus (MRSA) strains being a major contributor in both community and hospital settings. S. aureus relies on metabolic diversity and a large repertoire of virulence factors to cause disease. This includes α-hemolysin (Hla), an integral player in tissue damage found in various models, including SSTIs. Previously, we identified a role for the Spx adapter protein, YjbH, in the regulation of several virulence factors and as an inhibitor of pathogenesis in a sepsis model. In this study, we found that YjbH is critical for tissue damage during SSTI, and its absence leads to decreased proinflammatory chemokines and cytokines in the skin. We identified no contribution of YjbI, encoded on the same transcript as YjbH. Using a combination of reporters and quantitative hemolysis assays, we demonstrated that YjbH impacts Hla expression and activity both in vitro and in vivo. Additionally, expression of Hla from a non-native promoter reversed the tissue damage phenotype of the ΔyjbIH mutant. Lastly, we identified reduced Agr activity as the likely cause for reduced Hla production in the ΔyjbH mutant. This work continues to define the importance of YjbH in the pathogenesis of S. aureus infection as well as identify a new pathway important for Hla production.
Insights
The Spx adapter protein YjbH is crucial for Staphylococcus aureus skin infections, regulating tissue damage and alpha-hemolysin (Hla) production. Its absence reduces inflammation and virulence in skin and soft tissue infections (SSTIs).
Area of Science:
- Microbiology
- Infectious Diseases
- Molecular Biology
Background:
- Staphylococcus aureus is a leading cause of skin and soft tissue infections (SSTIs).
- Methicillin-Resistant S. aureus (MRSA) is a significant public health concern in both community and hospital settings.
- Alpha-hemolysin (Hla) is a key virulence factor contributing to S. aureus-mediated tissue damage.
Purpose of the Study:
- To investigate the role of the Spx adapter protein YjbH in S. aureus pathogenesis, specifically in SSTIs.
- To elucidate the mechanisms by which YjbH influences virulence factor expression and activity.
- To determine the contribution of YjbH and its associated protein YjbI to S. aureus-induced tissue damage.
Main Methods:
- Utilized reporter assays and quantitative hemolysis assays to assess Hla expression and activity.
- Employed mouse models of SSTIs to evaluate the in vivo role of YjbH.
- Generated and analyzed S. aureus mutants lacking YjbH and/or YjbI.
- Investigated the impact of YjbH on proinflammatory cytokine and chemokine levels in infected tissues.
Main Results:
- YjbH is critical for tissue damage in S. aureus SSTIs, with its absence leading to reduced inflammation.
- YjbH significantly impacts both the expression and activity of alpha-hemolysin (Hla) in vitro and in vivo.
- Absence of YjbH resulted in decreased production of proinflammatory chemokines and cytokines in the skin.
- Re-expression of Hla from a heterologous promoter restored the tissue damage phenotype in YjbH-deficient mutants.
- Reduced Agr activity was identified as the underlying cause for diminished Hla production in YjbH mutants.
Conclusions:
- YjbH plays a vital role in S. aureus pathogenesis, particularly in SSTIs, by regulating Hla production and activity.
- The study identifies a novel pathway involving YjbH that is important for controlling Hla expression.
- Understanding YjbH's function provides new insights into S. aureus virulence mechanisms and potential therapeutic targets.
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