Novel IgG-Degrading Enzymes of the IgdE Protease Family Link Substrate Specificity to Host Tropism of Streptococcus Species

Abstract

Recently we have discovered an IgG degrading enzyme of the endemic pig pathogen S. suis designated IgdE that is highly specific for porcine IgG. This protease is the founding member of a novel cysteine protease family assigned C113 in the MEROPS peptidase database. Bioinformatical analyses revealed putative members of the IgdE protease family in eight other Streptococcus species. The genes of the putative IgdE family proteases of S. agalactiae, S. porcinus, S. pseudoporcinus and S. equi subsp. zooepidemicus were cloned for production of recombinant protein into expression vectors. Recombinant proteins of all four IgdE family proteases were proteolytically active against IgG of the respective Streptococcus species hosts, but not against IgG from other tested species or other classes of immunoglobulins, thereby linking the substrate specificity to the known host tropism. The novel IgdE family proteases of S. agalactiae, S. pseudoporcinus and S. equi showed IgG subtype specificity, i.e. IgdE from S. agalactiae and S. pseudoporcinus cleaved human IgG1, while IgdE from S. equi was subtype specific for equine IgG7. Porcine IgG subtype specificities of the IgdE family proteases of S. porcinus and S. pseudoporcinus remain to be determined. Cleavage of porcine IgG by IgdE of S. pseudoporcinus is suggested to be an evolutionary remaining activity reflecting ancestry of the human pathogen to the porcine pathogen S. porcinus. The IgG subtype specificity of bacterial proteases indicates the special importance of these IgG subtypes in counteracting infection or colonization and opportunistic streptococci neutralize such antibodies through expression of IgdE family proteases as putative immune evasion factors. We suggest that IgdE family proteases might be valid vaccine targets against streptococci of both human and veterinary medical concerns and could also be of therapeutic as well as biotechnological use.

Antibiotic susceptibility, cytotoxicity, and protease activity of viridans group streptococci causing endophthalmitis

“…suis and S . porcinus [44]. We did not detect general protease activity in E618 by gelatin zymography; however, lack of detection by this assay does not exclude the possibility of IgG-degrading activity.…”

Characterization of therapeutic antibody fragmentation using automated capillary western blotting as an orthogonal analytical technique

“…A). This method was used to generate and purify the Fc fragment . The samples spiked with purified Fc had two enriched peaks at 15.2 and 16.3 min in the CE‐SDS electropherograms (Fig.…”

Streptococcus pseudoporcinus: Case Reports and Review of the Literature

“…However, one case report documented a multidrug-resistant S. pseudoporcinus isolate [3]. An IgG-degrading enzyme designated as IgdE was recently discovered that is highly specific for members of some of the Streptococcus species [7]. e S. pseudoporcinus IgdE protease appears to have specificity towards human IgG.…”

“…e S. pseudoporcinus IgdE protease appears to have specificity towards human IgG. e cleavage of the IgG subtypes might be a contributing factor for evading key immune defense mechanisms and progression to invasive disease [7].…”