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.
Highlights
Staphylococcus aureus is a potent human pathogen causing various medical conditions, from minor skin infections (i.a. pimples, impetigo, abscesses) to life-threatening diseases (i.a. bacteraemia, endocarditis and sepsis) [1]
Involvement of PantonValentine leukocidin (PVL) in the virulence of S. aureus has been a controversial topic for many scientists searching for factors responsible for the high pathogenicity of community associated S. aureus strains
Inasmuch as murine models have been delivering inconclusive results on the PVL contribution to the staphylococcal skin infections, we examined the role of this toxin using a rabbit an animal species whose neutrophils are as sensitive to the action of PVL as those of humans [18]
Summary
Staphylococcus aureus is a potent human pathogen causing various medical conditions, from minor skin infections (i.a. pimples, impetigo, abscesses) to life-threatening diseases (i.a. bacteraemia, endocarditis and sepsis) [1]. Subsequent in vivo experiments using murine models failed to uniformly prove the PVL contribution to the development of staphylococcal skin infections [14,15,16,17]. The reason for this inconsistency has been linked to a species-specific susceptibility of the host cells to PVL [18,19]. Since neutrophils isolated from mice have been reported to be relatively insensitive to the leukotoxic effect of PVL in contrast to human and rabbit cells [2,18], the latter has been postulated to be a better model for studying the role of PVL [18,19]
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