title: The streptococcal cysteine protease SpeB is not a natural immunoglobulin-cleaving enzyme.
abstract: The human bacterial pathogen Streptococcus pyogenes has developed a broad variety of virulence mechanisms to evade the actions of the host immune defense. One of the best-characterized factors is the streptococcal cysteine protease SpeB, an important multifunctional protease that contributes to group A streptococcal pathogenesis in vivo. Among many suggested activities, SpeB has been described to degrade various human plasma proteins, including immunoglobulins (Igs). In this study, we show that SpeB has no Ig-cleaving activity under physiological conditions and that only Igs in a reduced state, i.e., semimonomeric molecules, are cleaved and degraded by SpeB. Since reducing conditions outside eukaryotic cells have to be considered nonphysiological and IgG in a reduced state lacks biological effector functions, we conclude that SpeB does not contribute to S. pyogenes virulence through the proteolytic degradation of Igs.
authors.affiliation: Department of Molecular Biology, Umeå Centre of Microbial Research, Umeå University, Umeå, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Persson
authors.forename: Reine
authors.initials: R
authors.lastname: Vindebro
authors.forename: Ulrich
authors.initials: U
authors.lastname: von Pawel-Rammingen
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D005098:Exotoxins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism*; D009504:Neutrophils / Q000502:physiology; D010949:Plasma; D013297:Streptococcus pyogenes / Q000201:enzymology* / Q000472:pathogenicity; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D001798:Blood Proteins; D005098:Exotoxins; D007074:Immunoglobulin G; C027951:erythrogenic toxin