Drosophila melanogaster as a model to explore the effects of methicillin-resistant Staphylococcus aureus strain type on virulence and response to linezolid treatment

Background: USA300 is a uniquely successful methicillin-resistant Staphylococcus aureus (MRSA) clone that has been associated with Panton-Valentine leukocidin (PVL) production and severe infections. However, conflicting experimental and epidemiological data exist regarding the virulence of USA300 relative to other MRSA clones. We aimed to address this issue using Drosophila melanogaster as a model host to study strain and PVL-dependent variations in virulence among MRSA clinical isolates. Results: We studied the relative virulence of 39 MRSA isolates: 17 (43%) were PFGE type USA300. Lethal MRSA infection was reproducibly induced both in wild-type (WT) and Toll-deficient D. melanogaster. USA300 strains had significantly lower lethality than non-USA300 strains in a WT background but not in Toll-deficient flies. PFGE type (USA300 versus non-USA300) and PVL status did not affect the response to treatment with linezolid. Virulence was similar in strains with high vancomycin MIC (≥2 μg/mL) versus those with vancomycin MIC<2 μg/mL. Conclusions: D. melanogaster is a potentially useful model host to study pathogenicity and response to antibiotic treatment in S. aureus. Our results imply that the attenuated virulence of PVL⁺/USA300 requires intact host innate immunity.