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Updated: May 4, 2026
Experimental Endocarditis Model of Methicillin Resistant Staphylococcus aureus MRSA in Rat
Published on: June 4, 2012
α-Hemolysin, not Panton-Valentine leukocidin, impacts rabbit mortality from severe sepsis with methicillin-resistant
Anne-Claude Crémieux1, Azzam Saleh-Mghir, Claire Danel
1Département de Médecine Aigüe Spécialisée, Hôpital Universitaire Raymond-Poincaré, Assistance Publique-Hôpitaux de Paris, Garches.
Background:
Severe sepsis, combining acute osteomyelitis and lung involvement, has been described increasingly in healthy children with the spread of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA).
Methods:
Outcomes (mortality, hematogenous spread, lung and bone involvements) of rabbit osteomyelitis caused by CA-MRSA LAC(WT) USA300 and its Panton-Valentine leukocidin (PVL)- and α-hemolysin (Hla)-negative isogenic derivatives (LACΔpvl and LACΔhla, respectively) were compared.
Results:
Three days after inoculation (D3), all LAC(WT)- and LACΔpvl-, and 72% of LACΔhla-infected rabbits had no hematogenous spread and similar lung and bone bacterial densities. LACΔpvl and LACΔhla caused less severe histological lung lesions than LAC(WT) (P ≤ .01). Between D3 and D9, 10 (53%) LAC(WT)-, 11 (55%) LACΔpvl-, but no LACΔhla-infected rabbits (P < .005) died of severe sepsis with disseminated infection. Unlike deceased animals, most LAC(WT), LACΔpvl, and LACΔhla D14 survivors had no hematogenous spread (P < .001). LAC(WT) (88%) caused more bone abscesses than LACΔpvl (0, P = .001) or LACΔhla (30%, P = .01).
Conclusion:
In this model, both PVL and Hla seemed to be required for early lung involvement via hematogenous spread. Hla, but not PVL, significantly impacted severe sepsis-related mortality. PVL was the predominant factor determining late-stage bone abscesses.
Insights
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) causes severe sepsis in children. This study found Panton-Valentine leukocidin (PVL) and α-hemolysin (Hla) contribute differently to lung and bone infections, with Hla impacting mortality and PVL affecting bone abscesses.
Area of Science:
- Microbiology
- Infectious Diseases
- Pathogenesis
Background:
- Severe sepsis, encompassing osteomyelitis and lung involvement, is increasingly recognized in healthy children.
- Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a growing concern in pediatric infections.
Purpose of the Study:
- To investigate the roles of Panton-Valentine leukocidin (PVL) and α-hemolysin (Hla) in CA-MRSA-induced severe sepsis, osteomyelitis, and lung involvement in a rabbit model.
- To compare the outcomes of infections caused by wild-type CA-MRSA and its isogenic derivatives lacking PVL or Hla.
Main Methods:
- Comparison of osteomyelitis outcomes in rabbits infected with CA-MRSA USA300 (LAC(WT)) and its PVL-negative (LACΔpvl) and Hla-negative (LACΔhla) isogenic mutants.
- Assessment of mortality, hematogenous spread, lung and bone bacterial densities, histological lung lesions, and bone abscess formation.
Main Results:
- Both PVL and Hla were implicated in early lung involvement through hematogenous spread.
- Hla significantly influenced severe sepsis-related mortality, while PVL did not.
- PVL emerged as the primary factor in the development of late-stage bone abscesses.
Conclusions:
- Hla is crucial for severe sepsis mortality in this CA-MRSA osteomyelitis model.
- PVL plays a significant role in the formation of bone abscesses.
- Both toxins contribute to the pathogenesis of severe sepsis and disseminated infection caused by CA-MRSA.
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