Panton-Valentine Leukocidin Does Play a Role in the Early Stage of Staphylococcus aureus Skin Infections: A Rabbit Model

Abstract

Despite epidemiological data linking necrotizing skin infections with the production of Panton-Valentine leukocidin (PVL), the contribution of this toxin to the virulence of S. aureus has been highly discussed as a result of inconclusive results of in vivo studies. However, the majority of these results originate from experiments using mice, an animal species which neutrophils - the major target cells for PVL - are highly insensitive to the action of this leukocidin. In contrast, the rabbit neutrophils have been shown to be as sensitive to PVL action as human cells, making the rabbit a better experimental animal to explore the PVL role. In this study we examined whether PVL contributes to S. aureus pathogenicity by means of a rabbit skin infection model. The rabbits were injected intradermally with 108 cfu of either a PVL positive community-associated methicillin-resistant S. aureus isolate, its isogenic PVL knockout or a PVL complemented knockout strain, and the development of skin lesions was observed. While all strains induced skin infection, the wild type strain produced larger lesions and a higher degree of skin necrosis compared to the PVL knockout strain in the first week after the infection. The PVL expression in the rabbits was indirectly confirmed by a raise in the serum titer of anti-LukS-PV antibodies observed only in the rabbits infected with PVL positive strains. These results indicate that the rabbit model is more suitable for studying the role of PVL in staphylococcal diseases than other animal models. Further, they support the epidemiological link between PVL producing S. aureus strains and necrotizing skin infections.

Novel Phenol-soluble Modulin Derivatives in Community-associated Methicillin-resistant Staphylococcus aureus Identified through Imaging Mass Spectrometry

“…Soon after the emergence of CA-MRSA, the pore-forming cytotoxin Panton-Valentine leukocidin, present in many strains, was suggested to be the critical underlying determinant of infection (7). Controversy has arisen surrounding this proposal since murine models of infection using isogenic Panton-Valentine leukocidin-deficient CA-MRSA strains failed to show conclusive virulence contributions (8), and the role Panton-Valentine leukocidin plays in the infectious cycle of CA-MRSA continues to be examined in differential infection models with differing results (9).…”

Infección grave por Staphylococcus aureus meticilino sensible productor de leucocidina de Panton-Valentine: reportes de dos casos

“…Los autores concluyeron que múltiples factores diferentes de la PVL estarían asociados a la gravedad de las infecciones producidas por Sa. 3,4 Wehrhahn et al, observaron que la producción de toxinas diferentes a la PVL se asoció a infecciones de mayor gravedad por Sa en adultos. Las infecciones causadas por SaMS fueron más graves que las producidas por SaMR.…”

“…2 Ha sido relacionada con cuadros de miositis graves y neumonía necrotizante. 3,4 Estudios de epidemiología molecular realizados en nuestro medio han identificado la PVL en Staphylococcus aureus meticilino resistente (SaMR) y en Staphylococcus aureus meticilino sensible (SaMS). 5 Se presentan, a continuación, dos niños hospitalizados en el Hospital de Pediatría "Prof. Dr. Juan P. Garrahan" con infecciones graves por SaMS productores de PVL.…”

Methicillin-resistant Staphylococcus aureus antibiotic resistance and virulence

“…The first is that even in strains without PVL genes , virulence is still strong (76). The second is that isogenic PVL gene deletion mutants did not decrease the CA-MRSA virulence in a few animal models (77,78).…”