Staphylococcus sciuri Exfoliative Toxin C (ExhC) is a Necrosis-Inducer for Mammalian Cells

Abstract

Staphylococcus sciuri (S. sciuri) is a rare pathogen in humans, but it can cause a wide array of human infections. Recently a S. sciuri isolate (HBXX06) was reported to cause fatal exudative epidermitis (EE) in piglets and thus considered as a potential zoonotic agent. To investigate the pathogenicity of this bacterium, we cloned exfoliative toxin C (ExhC), a major toxin of the S. sciuri isolate and performed functional analysis of the recombinant ExhC-his (rExhC) protein using in vitro cell cultures and newborn mice as models. We found that rExhC could induce necrosis in multiple cell lines and peritoneal macrophages as well as skin lesions in newborn mice, and that the rExhC-induced necrosis in cells or skin lesions in newborn mice could be completely abolished if amino acids 79-128 of rExhC were deleted or blocked with a monoclonal antibody (3E4), indicating aa 79-128 portion as an essential necrosis-inducing domain. This information contributes to further understandings of the mechanisms underlying S. sciuri infection.

Pathogenicity of Staphylococcus sciuri in murine in vivo model

“…The histopathological changes in form of dermal abscess in the skin and microabscess in liver, may suggest that the organism invaded the organs and caused necrosis which triggered formation of the abscesses. Dermal abscesses are not uncommon findings in Staphylococcus aureus infection, and exfoliative toxin C (ExhC) of S. sciuri has been suggested to be a mammalian necrosis inducer (Li et al, 2011). This might be the first report of dermal abscess associated with S. sciuri containing exfoliative toxin A gene.…”

Critical roles of amino acids Ser231, His107 and Asp156 of Staphylococcus sciuri exfoliative toxin C (ExhC) in the induction of skin exfoliations in neonate mice

“…In our previous study, we found that the ExhC (GenBank accession No. JF755400) from S. sciuri HBXX06 is identical to that of S. hyicus in GenBank (AF515455), and that recombinant ExhC expressed in E. coli BL21 cause necrosis in BHK-21 cells and skin lesions in newborn mice (Li et al 2011). In this study, we predicted the three-dimensional structure of S. sciuri HBXX06 ExhC and replaced Ser231, His107, Asp156 of ExhC, and found that mutant ExhC would lose the activity of inducing skin lesions in newborn mice if any one of those amino acid residues in the active site was changed.…”

“…In our previous study, we found that recombinant ExhC caused necrosis in BHK-21 cells (Li et al 2011), thus we use BHK-21 as a model to examine the effects of mutant ExhC on cultured cells. We found that treatment of BHK-21 cells with both mutant ExhC and wild-type ExhC could cause cell death, whereas cells in the controls grew well (Fig.…”

Staphylococcus sciuri associated to subcutaneous abscess and dermatitis in ICR mouse

“…Recently, S. sciuri strain HBXX06 (carry exfoliate toxin: ExhC) was reported as highly pathogenic when inoculated in piglets and BALB/c mice and caused fatal exudative epidermitis (Chen et al, 2007). This toxin induces severe skin lesion in new borne mice, especially blisters, exfoliation, and tissue necrosis (Li et al, 2011a;Li et al, 2011b). These may emphasize a highly heterogeneous S. sciuri, the prevalence study of genotyping among subgroup will be required to elucidate the understanding of its natural history.…”

“…Moreover S. sciuri has been associated with serious infections in humans such as endocarditis, peritonitis, septic shock, and wound infections (Hedin and Widerstrom, 1998;Stepanovic et al, 2000;Wallet et al, 2000;Horii et al, 2001), however the incidence is merely rare (Li et al, 2011b). Similar to the incidence in the laboratory animal species, nevertheless, the infection with S. sciuri commonly plays commensal of oral cavity in rodent species e.g.…”