Molecular Dissection of the Pathogenesis of Highly Pathogenic Infections by Streptococcus Suis Serotype 2
|School||Nanjing Medical University|
|Keywords||Suis type 2 ( SS2 ) Streptococcal toxic shock syndrome ( STSS ) Whole-genome sequencing Genomic Island Pathogenicity island sortase enzyme Knockout|
Suis type 2 (Streptococcus suis serotype 2, SS2) is an important zoonotic pathogens. SS2 infection can be caused by a swine model of acute sepsis, meningitis, arthritis, endocarditis, and acute death, and can lead to the pathogenesis of human infection through wounds and other routes of transmission, the typical clinical symptoms of meningitis, septicemia, arthritis and other. The disease has a worldwide distribution, not only causing huge economic losses to the swine industry worldwide, but also pose a serious threat to the health of practitioners, has become an important emerging pathogens of infectious diseases. 1998 and 2005, China's Jiangsu Province and Sichuan Province epidemic outbreak of large-scale SS2 infection, patients with a high proportion of rare at home and abroad streptococcal toxic shock syndrome (streptococcal toxic shock syndrome, STSS), presents a high invasion, deep tissue infection is characterized by dangerous disease, high mortality (81.3% to 97.4%), breaking the STSS past that they were all caused by group A streptococcus (GAS) this limitation, caused worldwide concern, but SS2 cause STSS The molecular mechanism is not clear. Systematic analysis of the molecular basis of the different sources and pathogenic SS2 differences, we targeted acquisition Jiangsu endemic areas of healthy pigs tonsil swabs and dissemination of infected patients cerebrospinal fluid samples the SS2 isolation and identification of the results of each isolated one SS2 separation time and sources were named 05JYS68 and 07NJH06. System Pathogen Biology the identification found 05JYS68 missing the virulence factor extracellular factor (EF), hemolysin (Sly), their natural host pig does not have the pathogenic strains is a natural; 07NJH06 strain recently from the distribution encephalitis separation of human pathogenic strains, virulence than the previous domestic outbreaks field isolates weak basic biological characteristics, virulence genotypes and strong domestic the pathogenic strains 05ZYH33 no significant differences in the genome does not contain the full virulence Island PAI89k. The separation of the strains to carry out comparative genomics research to reveal the molecular mechanisms of pathogenicity and common nature SS2 genetic evolution path as well as strong domestic pathogenic plant height invasion force laid the foundation. Our group popular in Jiangsu in 1998 virulent strains 98HAH12 of Sichuan popular strong the pathogenic strains 05ZYH33 (two patients) were isolated from the STSS 2005 isolated from Jiangsu the avirulent health of pigs carrying strains 05JYS68 whole-genome sequencing and functional annotation, 3 Genome and Sanger Research Center published standard strain P1 / 7 genome sequence and comparative genomic analysis. The study found that the three SS2 performance of two evolutionarily evolved independently segregating lines, each unique parasitic habitat is segregating lines to the power of adaptive evolution. At the same time, in 98HAH12 and 05ZYH33 genome unexpectedly found a length of 89 kb fragment further bioinformatics and experimental analysis showed that the fragment is unique to the virulent strains, and is fully equipped with pathogen virulence Island (pathogenicity islands Pais) the basic characteristics of the named to PAI89K. These results suggest that PAI89K fragment may SS2 obtained by horizontal gene transfer pathogenicity island, making the the originally avirulent or attenuated strains of force \PAI89K found so far Streptococcus suis candidate pathogenicity island, its findings will help reveal the the SS2-induced STSS molecular basis, the level of functional genomics and provide a scientific basis for infection prevention and control of highly pathogenic SS2 . With bioinformatics software systems analysis and distribution of membrane proteins anchored the source virulent strains 05ZYH33 genome the number of enzyme the Sortase-coding genes (SRT), were found in six srt gene homologous sequences (the Srta - F), which SrtA attributable to the classic group A \It is noteworthy that, SrtBCD SrtF with varying amounts of membrane-anchored protein formed adjacent to the two gene clusters, gene structure and Gram-positive pathogens (such as Streptococcus pyogenes GAS, Streptococcus pneumoniae, Corynebacterium diphtheria and saliva chain cocci GBS) pili gene structure features are exactly the same, SS2 pili coding gene cluster, named the clusters of SrtBCD gene and SrtF gene cluster. \, the The mutant ΔsrtA surface missing the classic film surface protein MRP and Sao, the adhesion ability of human vascular endothelial cells and epithelial cells (HUVEC and Hep-2) than the wild-type strain was significantly decreased (p lt; 0.01), experimental infection of pigs after the colonization of tissues with varying degrees of decline, and also decrease the morbidity and mortality of infected animals. These results showed that the The sortase A SS2 important membrane surface proteins (such as MRP, Sao) GGT, it may be by acting on the substrate membrane proteins in bacterial adhesion and invasion of host tissue cells, thus pathogenic bacteria impact.