| Group A Streptococcus (GAS) is responsible for various human suppurative and nonsuppurative infections. Suppurative infections include pharyngitis, scarlet fever, impetigo and cellulitis. Nonsuppurative infections include acute rheumatic fever and acute glomerulonephritis. Acute glomerulonephritis (AGN) is an acute nephritic syndrome characterized by the sudden appearance of edema, hematuria, proteinuria, and hypertension, and is the most common nephritis among children. It has been more clearly that the mechanisms of deposition of immune complex are contributed to a majority of AGN cases.Several APSGN outbreaks have been reported in recent years in China. The most serious outbreaks happened in Nov 2005 in Guizhou province, which affected two adjacent counties,11 townships and several primary schools. There are sixty-two cases reported from the emergency public health events reporting system in total, two of them died. Following epidemiologic investigation and experimental pathogenic analysis performed by China CDC indicate the outbreaks are associated with the infection of group A streptococcus. To further investigate the molecular characteristic of GAS strains associated with the outbreaks, Zheng Minghuan et al performed multiple typing methods including emm, sof, PFGE, MLST for the molecular typing of sixty-eight isolates. The molecular epidemiologic analysis indicates emm60.1 and emm63.0 are the two dominant types responsible for the outbreaks. The results of epidemiologic investigation suggest that crowded resident and sub-optimal hand-washing are associated with increased risk for APSGN. However, the pathogenesis is still unclear. To gain an enhanced understanding of the pathogenesis of APSGN and the potential genetic characterization of the pathogen contributed to the outbreaks, as well as based on the data obtained by previously performed molecular typing, six nephritis and non-nephritis associated strains are selected to initiate a genome sequencing by illumina/solexa analyzer. All sequences are intra-aligned and aligned to the multiple whole genome sequences avaiable online. Several distinct genes are obtained by aligning genomes with different phenotypes and genotypes. A sil locus associated with quorum sensing regulon was found in the strains of nephritogenic emm60, one of the predominant emm type responsible for the outbreaks, the locus is absent in the non-nephritogenic emm60 strain. The study speculate that the locus probably function as a regulator controling the expression of some virulence genes, further affect the ability of strain virulence. The study showed prophages and insertion elements still represent important and a majority of plasticity regions in GAS chromosome. In addition, this study performed comparative sequence analysis of FCT regions, which encode a variety of cell wall anchored surface proteins and T antigens. Many studies speculate that gene products of GAS in FCT region may have key roles in pathogenesis by mediating bacterial adherence to host tissue. The study showed that the predominant strains in this outbreak represented a FCT-5 type, and sporadic strains represented FCT-1 and-6 type. The special gene forms and combinations in the two type strains suggest a distinct virulence associated with the AGN outbreak. Genetic differences between isolations of east and west were also obtained based on an overall alignment of all sequences available. Genes associated with iron and Glycerol uptake, sos response were found between the two type strains. The data in this study provide useful molecular genetic informations for exploring the mechanism of post streptococcal glomerulonephritis. |
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