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Vancomycin-intermediate Staphylococcus aureus isolates are attenuated for virulence when compared with susceptible
D R Cameron1, Y-H Lin2, S Trouillet-Assant3
1Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Australia.
Summary
Vancomycin-intermediate Staphylococcus aureus (VISA) exhibits reduced virulence and immune evasion compared to susceptible strains. VISA strains are less cytotoxic, persist intracellularly, and cause lower mortality, indicating adaptation for persistent infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Molecular Biology
Background:
- Vancomycin-intermediate Staphylococcus aureus (VISA) emergence poses a significant clinical challenge.
- Genetic modifications in VISA may influence pathogenicity and virulence factors.
- Understanding VISA virulence is crucial for effective treatment strategies.
Purpose of the Study:
- To compare the virulence of clinical VISA strains against their vancomycin-susceptible progenitor strains (VSSA).
- To investigate the impact of genetic changes on alpha-toxin production and agr activity.
- To evaluate the role of non-professional phagocytes (NPP) in VISA persistence.
Main Methods:
- Western blot analysis for alpha-toxin quantification.
- Bioluminescent agr-reporter assay for agr activity assessment.
- Ex vivo comparison of cytotoxicity and intracellular persistence in NPP.
- In vivo murine bacteraemia model to assess virulence and host immune response.
Main Results:
- VISA isolates produced significantly lower levels of alpha-toxin (up to 20-fold less) compared to VSSA.
- VISA exhibited reduced cytotoxicity towards NPP but enhanced intracellular persistence, suggesting NPP as a potential reservoir.
- Infection with VSSA resulted in higher mortality (≥90%) than VISA (20-50%) in a murine model, with VISA inducing a dampened immune response (reduced IL-6) and persistent organ colonization.
Conclusions:
- VISA strains demonstrate remarkable adaptability, altering virulence factor expression to evade host immunity.
- This adaptation favors persistent infection over acute virulence, highlighting a survival strategy beyond antibiotic resistance.
- Findings underscore the complex interplay between antibiotic resistance and pathogenicity in Staphylococcus aureus.