Role of Surface Protective Antigen A in the Pathogenesis of Erysipelothrix rhusiopathiae Strain C43065

Abstract

To clarify the role of surface protective antigen A (SpaA) in the pathogenesis of Erysipelothrix rhusiopathiae C43065 (serotype 2), the spaA deletion mutant of E. rhusiopathiae ΔspaA was constructed by homologous recombination. The virulence of the ΔspaA mutant decreased more than 76-fold compared with that of the wild-type strain C43065 in mice. The mutant strain was sensitive to the bactericidal action of swine serum, whereas the wild-type strain was resistant. The adhesion of wild-type strain to MEF cells was inhibited significantly by treatment with rabbit antiserum against recombinant SpaA (rSpaA) as compared with the treatment with normal rabbit serum, but the mutant strain was not affected. The mutant strain was readily taken up by mouse peritoneal macrophages in the normal rabbit serum, whereas the wild-type strain was resistant. Whereas the rabbit antiserum against rSpaA promoted the phagocytosis of wild-type strain by macrophages, the mutant strain was not affected. In addition, mice vaccinated with the formalin-killed mutant strain were provided 40% protection against challenge by the homologous virulent strain as compared with those with wild-type strain, NaOH-extracted antigen, or rSpaA, which provided more than 80% protection against the same infection. These suggested that SpaA has an important role in the pathogenesis of E. rhusiopathiae infection and could be a target for vaccination against swine erysipelas.

Genomic and Immunogenic Protein Diversity of Erysipelothrix rhusiopathiae Isolated From Pigs in Great Britain: Implications for Vaccine Protection

“…We found that the amino acid sequence of the E. rhusiopathiae SpaA protein predicts a protein structure most closely resembling that of choline-binding proteins of Streptococcus pneumoniae. Indeed, the homology in the C-terminal region of these proteins had previously been described (Borrathybay et al, 2015). This region -containing tandem repeats including the GW motif -is a motif conserved across Gram-positive bacteria that allows proteins to bind to choline residues of techoic acid on the cell surface (Jedrzejas, 2001).…”

“…It has been shown that the N-terminal immunoprotective domain of this surface proteinalso referred to as the hypervariable domain -is the component responsible for eliciting protective immunity (Figure 1; Imada et al, 1999;Shimoji et al, 1999). SpaA also plays an important role in pathogenesis by increasing resistance to phagocytosis and promoting endothelial adherence (Harada et al, 2014;Borrathybay et al, 2015;Zhu et al, 2017a,b). Several variants (groups) of the SpaA protein have already been described, based on amino acid differences within the immunoprotective domain (Uchiyama et al, 2014;Janßen et al, 2015;Ogawa et al, 2017).…”

Characterization of spaC‐type Erysipelothrix sp. isolates causing systemic disease in ornamental fish

“…Virulence factor profiles of isolates from terrestrial animals are fairly uniform (Janßen et al, 2015) and include an immunologically significant surface-protective antigen (Spa) for which three isoforms, SpaA, SpaB and SpaC, have been identified (To & Nagai, 2007). SpaA is a common protective antigen of E. rhusiopathiae (Imada, Goji, Ishikawa, Kishima, & Sekizaki, 1999) and virulence determinant that plays a role in cell adhesion, as well as resistance to serum killing and phagocytosis by macrophages (Borrathybay, Gong, Zhang, & Nazierbieke, 2015).…”

Glyceraldehyde-3-phosphate dehydrogenase acts as an adhesin in Erysipelothrix rhusiopathiae adhesion to porcine endothelial cells and as a receptor in recruitment of host fibronectin and plasminogen

“…However, GAPDH is not the only adhesin of E. rhusiopathiae . Other adhesins, such as SpaA, RspA and RspB [23–25], have been reported. Thus, in the competitive adhesion inhibition assay the inhibition was only partial.…”