No abstract

Streptococcus pyogenes or group A Streptococcus (GAS) causes ~700 million human infections each year, resulting in over 500,000 deaths. The development of a commercial GAS vaccine is hampered due to high strain and serotype diversity in different geographical regions, and the generation of cross-reactive antibodies that may induce autoimmune disease. There is an urgent need to search for alternative vaccine candidates. High throughput multigenome data mining coupled with proteomics seems to be a promising approach to identify the universal vaccine candidates. In the present study, in silico analysis led to prediction of 147 proteins as universal vaccine candidates. Distribution pattern of these predicted candidates was explored in nonsequenced Indian GAS strains (n = 20) by using DNA array hybridization validating in silico analysis. High throughput analyses of surface proteins using 1D-SDS-PAGE coupled with ESI-LC-MS/MS was applied on highly (M49) and less (M1) invasive GAS strains of Indian origin. Comparative proteomics analysis revealed that highly invasive GAS M49 had metabolically more active membrane associated protein machinery than less invasive M1. Further, by overlapping proteomics data with in silico predicted vaccine candidate genes, 52 proteins were identified as probable universal vaccine candidates, which were expressed in these GAS serotypes. These proteins can further be investigated as universal vaccine candidates against GAS. Moreover, this robust approach may serve as a model that can be applied to identify the universal vaccine candidates in case of other pathogenic bacteria with high strain and genetic diversity.

Background:Pili have been shown to play a key role in the attachment. Results: Pilus proteins anti-SAN1518, GBS80, and GBS67 inhibited the adherence and invasion of GBS to the lung and cervical epithelial cells. Conclusion: Pilus protein contributes to the initial attachment and invasion of GBS. Significance: Pilus protein-based vaccine formulation can also be tested against GBS serotypes of India.

Introduction: In this study, the prevalence of M types of Group A Streptococcus (GAS) in North India, invasive behavior of prevalent M types, and inflammatory immune response by host cells were studied. Methodology: A total of 1,047 clinical samples were collected between 2004 and 2010. Confirmation of GAS was determined by serotyping and M types were identified by emm gene sequencing. The most prevalent serotypes were selected to study their invasive behavior and inflammatory immune response under different temperatures and salt concentrations in A549 and HEp-2 cells. Results: Ninety-two isolates were identified as GAS of which 17 were M types with 18.5% heterogeneity. The most prevalent M types were M1 (21.73%) and M49 (8.7%), respectively. M1 and M49 were used to study virulence potential and inflammatory immune responses. The efficiency of cell infection decreased with increased temperature for both M types, increasing with lowering temperatures compared to the uninfected control (37°C). As salt concentration was increased, cell infection efficiency was lowered with some exceptions; the infection efficiency of M1 strain in A549 cells with 0.6 M NaCl was 50 fold higher (p ≤ 0.03). Significantly increased production of IL-6 and IL-8 was observed in both cell lines infected with GAS and when grown under different environmental conditions compared to uninfected cell lines. Conclusions: This study determined the prevalence of different M types in North India and showed that environmental conditions can regulate cell infection by GAS . This information may influence the selection of GAS serotypes used in vaccine development.