Natural Variant of Collagen-Like Protein A in Serotype M3 Group A Streptococcus Increases Adherence and Decreases Invasive Potential

Group A Streptococcus (GAS) predominantly exists as a colonizer of the human oropharynx that occasionally breaches epithelial barriers to cause invasive diseases. Despite the frequency of GAS carriage, few investigations into the contributory molecular mechanisms exist. To this end, we identified a naturally occurring polymorphism in the gene encoding the streptococcal collagen-like protein A (SclA) in GAS carrier strains. All previously sequenced invasive serotype M3 GAS possess a premature stop codon in the sclA gene truncating the protein. The carrier polymorphism is predicted to restore SclA function and was infrequently identified by targeted DNA sequencing in invasive strains of the same serotype. We demonstrate that a strain with the carrier sclA allele expressed a full-length SclA protein, while the strain with the invasive sclA allele expressed a truncated variant. An isoallelic mutant invasive strain with the carrier sclA allele exhibited decreased virulence in a mouse model of invasive disease and decreased multiplication in human blood. Further, the isoallelic invasive strain with the carrier sclA allele persisted in the mouse nasopharynx and had increased adherence to cultured epithelial cells. Repair of the premature stop codon in the invasive sclA allele restored the ability to bind the extracellular matrix proteins laminin and cellular fibronectin. These data demonstrate that a mutation in GAS carrier strains increases adherence and decreases virulence and suggest selection against increased adherence in GAS invasive isolates.     

Therapeutic Effect of Dimethyl Dimethoxy Biphenyl Dicarboxylate on Collagen-Induced Arthritis in Rats

Objective:To study the effect of oral administration of dimethyl dimethoxy biphenyl dicarboxylate(DDB) on adjusting angiogeneic/inflammatory mediators and ameliorating the pathology of bones in rats with collagen-induced arthritis(CIA).Methods:Wistar rat model of CIA was set up using bovine collagen type Ⅱ.Fifty rats were divided into five groups randomly:normal,CIA model,DDB treatment,methotrexate(MTX) treatment,and combined DDB+MTX treatment.Ankle joints of rats were imaged with digital X-ray machine to show the destruction of joints.Fore and hind paw and knee joints were removed above the ankle joint then processed for haematoxylin and eosin staining.Plasma levels of vascular endothelial growth factor(VEGF),platelet derived growth factor,interleukin-8(IL-8),IL-4,tumor necrosis factor α(TNF-α),and cyclooxygenase-2(COX-2) were quantified by enzyme-linked immunosorbent assay.Nitric oxide levels were detected by Griess reagent.Results:Compared with the CIA model group,a remarkable reduction in various angiogenic(VEGF and IL-8) and inflammatory mediators(TNF-α,IL-4 and COX-2) after treatment with DDB either alone or combined with MTX(P0.05 or P0.01).Histopathological and X-ray findings were confirmatory to the observed DDB anti-arthritic effect.The DDB-treated group showed amelioration in signs of arthritis which appeared essentially similar to normal.Conclusion:Our data shed light on the therapeutic efficacy of DDB in experimental rheumatoid arthritis(RA) compared with a choice drug(MTX) and it may be offered as a second-line drug in the treatment of RA.