Comparative Analysis of USA300 Virulence Determinants in a Rabbit Model of Skin and Soft Tissue Infection

Abstract

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are frequently associated with strains harboring genes encoding Panton-Valentine leukocidin (PVL). The role of PVL in the success of the epidemic CA-MRSA strain USA300 remains unknown. Here we developed a skin and soft tissue infection model in rabbits to test the hypothesis that PVL contributes to USA300 pathogenesis and compare it with well-established virulence determinants: alpha-hemolysin (Hla), phenol-soluble modulin-alpha peptides (PSMα), and accessory gene regulator (Agr). The data indicate that Hla, PSMα, and Agr contribute to the pathogenesis of USA300 skin infections in rabbits, whereas a role for PVL could not be detected.

The adherens junctions control susceptibility to Staphylococcus aureus α-toxin

“…Chief among the arsenal of S. aureus virulence factors, α-toxin (or α-hemolysin) is a critical determinant for pathogenesis in a wide variety of experimental infections, particularly during epithelial infections such as skin abscesses and pneumonia (7)(8)(9)(10). After secretion as a soluble monomer, α-toxin oligomerizes on the targeted host cell surface via interactions with its high-affinity metalloprotease receptor, a disintegrin and metalloprotease 10 (ADAM10), forming a 1-3-nm pore that spans the cellular membrane lipid bilayer (11,12).…”

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

“…However, two experimental results cast a damper over the assumption. 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).…”

“…Cytolysin α-toxin greatly increases virulence of CA-MRSA in some animal models (76,80). The α-toxin was proven to significantly increase virulence by lysing a series of cells, such as macrophages and erythrocytes, and cause collapse of the epithelial barrier (81).…”