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Published on: March 14, 2019
Panton-valentine leukocidin enhances the severity of community-associated methicillin-resistant Staphylococcus aureus
Anne-Claude Crémieux1, Oana Dumitrescu, Gerard Lina
1Département de médecine aigüe, Hôpital Universitaire Raymond Poincaré, Assistance Publique-Hôpitaux de Paris, Garches, France.
Background:
Extensive spread of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in the United States, and the concomitant increase in severe invasive staphylococcal infections, including osteomyelitis, in healthy children, has led to renewed interest in Panton-Valentine leukocidin (PVL). However, the pathogenetic role of PVL in staphylococcal infections remains controversial, possibly because it depends on the site of infection.
Methodology/Principal Findings:
We compared the course of experimental rabbit osteomyelitis due to the PVL-positive CA-MRSA strain USA 300 (LAC) and its PVL-negative isogenic derivative (LACDeltapvl), using a low and a high inoculum (8x10(5) and 4x10(8) CFU). With the low inoculum, bone infection was less frequent on day 7 (D7) and day 28 (D28) with LACDeltapvl than with LAC (respectively 12/19 and 18/19 animals, p = 0.042). With the high inoculum of both strains, all the animals were infected on D7 and the infection persisted on D28 in almost every case. However, tibial bacterial counts and the serum CRP concentration fell significantly between D7 and D28 with LACDeltapvl but not with LAC. Respectively 67% and 60% of LAC-infected rabbits had bone deformation and muscle/joint involvement on D7, compared to 0% and 7% of LACDeltapvl-infected rabbits (p = 0.001 and p = 0.005 respectively). Between D0 and D28, the anti-PVL antibody titer increased significantly only with the high inoculum of LAC.
Conclusions/Significance:
PVL appears to play a role in the persistence and rapid local extension of rabbit osteomyelitis, in keeping with the greater severity of human bone infections due to PVL-positive S. aureus. The possible therapeutic implications of these findings are discussed.
Insights
Panton-Valentine leukocidin (PVL) contributes to severe staphylococcal osteomyelitis in rabbits. PVL-positive strains caused more persistent infections and bone damage than PVL-negative strains.
Area of Science:
- Microbiology
- Infectious Diseases
- Pathogenesis
Background:
- Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is increasing.
- Severe invasive staphylococcal infections, including osteomyelitis, are rising in children.
- The role of Panton-Valentine leukocidin (PVL) in staphylococcal infections is debated.
Purpose of the Study:
- To investigate the role of PVL in experimental rabbit osteomyelitis.
- To compare the pathogenicity of PVL-positive and PVL-negative CA-MRSA strains.
Main Methods:
- Experimental rabbit osteomyelitis model using PVL-positive (LAC) and PVL-negative (LACDeltapvl) CA-MRSA strains.
- Inoculation with low (8x10^5 CFU) and high (4x10^8 CFU) bacterial doses.
- Assessment of infection frequency, bacterial load, serum CRP, bone deformation, and anti-PVL antibody titers.
Main Results:
- PVL-positive strains caused more frequent and persistent bone infections, especially with low inocula.
- High inocula of both strains led to persistent infection, but PVL-negative strains showed reduced bacterial counts and CRP levels over time.
- PVL-positive strains were associated with significantly higher rates of bone deformation and muscle/joint involvement.
Conclusions:
- PVL contributes to the persistence and local spread of staphylococcal osteomyelitis.
- Findings align with the increased severity of human bone infections caused by PVL-positive S. aureus.
- Potential therapeutic strategies targeting PVL may be beneficial.
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