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Updated: Sep 16, 2025
A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
Published on: February 28, 2019
Staphylococcus aureus LukMF' targets neutrophils to promote skin and soft tissue infection
Daiane Boff1, Ravishankar Chandrasekaran2, Gregory Putzel3
1Department of Microbiology, New York University Grossman School of Medicine, New York, NY, USA.
Abstract:
Pathogens have evolved to be highly adapted to their natural host. Community-associated methicillin-resistant Staphylococcus aureus USA300, for instance, is a lineage responsible for the epidemic of skin and soft tissue infections (SSTIs) in humans. Owing to its human tropism, mechanisms that enabled the rise of USA300 as a major skin pathogen remain incompletely defined. By leveraging a rodent-adapted strain of S. aureus, we developed a natural model of SSTIs. We found that LukMF', a pore-forming leukocidin homolog to the human-specific LukSF-PV toxin, drives skin pathology in mice. LukMF' lyses neutrophils via the chemokine receptor CCR1, which in turn fuels inflammatory pathology and microbial survival within the infectious nidus. Ablation of CCR1, depletion of neutrophils, or vaccination with LukMF' all protected mice from skin pathology. Thus, these data support epidemiological studies linking leukocidins with human SSTIs and highlight the power of natural models to unearth potential targets to curtail infections.
Insights
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) USA300 causes skin infections. A novel rodent model revealed that the leukocidin LukMF
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) USA300 is a major cause of human skin and soft tissue infections (SSTIs).
- The specific mechanisms driving USA300's success as a human skin pathogen are not fully understood.
- Understanding these mechanisms is crucial for developing effective treatments and prevention strategies.
Purpose of the Study:
- To investigate the mechanisms by which USA300 causes skin infections.
- To identify potential therapeutic targets for CA-MRSA SSTIs.
- To validate the utility of a natural host model for studying S. aureus pathogenesis.
Main Methods:
- Development of a natural mouse model of SSTIs using a rodent-adapted S. aureus strain.
- Investigation of the role of the leukocidin LukMF' in driving skin pathology.
- Analysis of the interaction between LukMF', neutrophils, and the chemokine receptor CCR1.
- Assessment of protective strategies including CCR1 ablation, neutrophil depletion, and vaccination with LukMF'.
Main Results:
- The leukocidin LukMF', a homolog of human-specific LukSF-PV, was identified as a key driver of skin pathology in the mouse model.
- LukMF' was shown to lyse neutrophils through the chemokine receptor CCR1, exacerbating inflammation and promoting bacterial survival.
- Blocking CCR1, depleting neutrophils, or vaccinating against LukMF' conferred significant protection against skin infection in mice.
Conclusions:
- The study highlights the critical role of LukMF' in mediating skin pathology during S. aureus infections.
- Neutrophils and their interaction with CCR1 are central to the inflammatory response and microbial persistence in SSTIs.
- Natural host models are powerful tools for dissecting pathogen virulence mechanisms and identifying novel therapeutic targets like LukMF' and CCR1.
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