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Development and Assessment of Intracellular Infection Models for Staphylococcus aureus
Published on: January 17, 2025
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Genome Plasticity of agr-Defective Staphylococcus aureus during Clinical Infection.
Deena R Altman1,2, Mitchell J Sullivan2, Kieran I Chacko2
1Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Infection and Immunity
|August 1, 2018
Summary
Staphylococcus aureus infections with defective agr function accumulate mutations, potentially increasing virulence. These genetic changes, independent of agr, can lead to persistent infections and poor patient outcomes.
Area of Science:
- Microbiology
- Genomics
- Infectious Diseases
Background:
- Therapy for Staphylococcus aureus bacteremia is often ineffective.
- Agr-defective subclones are linked to persistent infections and mortality.
Purpose of the Study:
- To identify genetic alterations in agr-defective Staphylococcus aureus mutants.
- To understand the adaptation and diversification of agr-defective strains during infection.
Main Methods:
- Whole-genome sequencing of S. aureus clone pairs from patients.
- Comparative genomic analysis of agr-defective and wild-type strains.
- Murine model of bloodstream infection and expression profiling.
Main Results:
- Agr-defective strains showed increased mutations compared to controls.
- Mutations were randomly distributed, suggesting therapy-induced stress or prolonged infection.
- One agr-defective mutant exhibited enhanced virulence in mice, linked to restored ESAT6 secretion.
Conclusions:
- Additional mutations outside the agr locus contribute to S. aureus adaptation and virulence.
- These adaptations in agr-defective mutants can lead to poor patient outcomes.
- Understanding these genetic changes is crucial for developing effective therapies against S. aureus infections.
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