Differences in SpeB protease activity among group A streptococci associated with superficial, invasive, and autoimmune disease

Abstract

The secreted cysteine proteinase SpeB is an important virulence factor of group A streptococci (GAS), whereby SpeB activity varies widely among strains. To establish the degree to which SpeB activity correlates with disease, GAS organisms were recovered from patients with pharyngitis, impetigo, invasive disease or acute rheumatic fever (ARF), and selected for analysis using rigorous sampling criteria; >300 GAS isolates were tested for SpeB activity by casein digestion assays, and each GAS isolate was scored as a SpeB-producer or non-producer. Highly significant statistical differences (p < 0.01) in SpeB production are observed between GAS recovered from patients with ARF (41.5% SpeB-non-producers) compared to pharyngitis (20.5%), invasive disease (16.7%), and impetigo (5.5%). SpeB activity differences between pharyngitis and impetigo isolates are also significant, whereas pharyngitis versus invasive isolates show no significant difference. The disproportionately greater number of SpeB-non-producers among ARF-associated isolates may indicate an altered transcriptional program for many rheumatogenic strains and/or a protective role for SpeB in GAS-triggered autoimmunity.

Neutrophil-derived reactive agents induce a transient SpeB negative phenotype in Streptococcus pyogenes

“…Experiments also included testing activity with addition of H 2 O 2 (10 and 100 µM). Furthermore, SpeB secretion and activity were tested via casein digestion assay as described previously [ 21 ]. Serial dilutions of bacteria were plated on modified Columbia agar containing 3% (w/v) skim milk (both Sigma-Aldrich) following incubation under 37 °C and 5% CO 2 atmosphere for 24 h. SpeB + producers were characterized by a clearance zone around the colonies, whereas non-producers had no zone of clearance.…”

Pathogenic mechanisms of invasive group A Streptococcus infections by influenza virus–group A Streptococcus superinfection

“…Many studies have suggested that GAS virulence factors, such as adhesin, invasin, enzymes that destroy host tissues and exotoxins are associated with development of the disease. SLO , SLS , SPEB , streptococcal C5a peptidase of GAS , fibronectin‐binding proteins , laminin‐binding proteins , collagen‐like proteins and hyaluronan capsules are candidates for development of invasive GAS infections. Mutations of covS and rgg , which encode negative transcriptional regulators in GAS, are also associated with invasive GAS infections .…”