Group A streptococcal infection in a mouse model: role of SPE B

• Main Authors: Hsiu Yueh Lin, 林秀月
• Other Authors: Yee-Shin Lin
• Format: Others
• Language: zh-TW
• Published: 1999
• Online Access: http://ndltd.ncl.edu.tw/handle/95326013936828972200

碩士 === 國立成功大學 === 微生物暨免疫學研究所 === 87 === Abstract Group A streptococci (GAS) streptococcus pyogenes causes a broad spectrum of diseases. Clinical features that result in life-threatening sequelae include necrotizing fasciitis and streptococcal toxic shock syndrome. However, so far, their pathogenic factors are poorly defined. Accumulated evidence suggests that streptococcal pyrogenic exotoxin B (SPE B) may be a critical virulent factor in invasive GAS infections. The gene of SPE B is found in all strains of GAS, and the encoded protein functions as a cysteine protease. In order to study the role that SPE B may play in the pathogenesis of GAS infection, the isogenic protease-negative mutants were previously constructed by homologous recombination. The common primary focuses of the severe GAS infections are infections of the skin and soft tissue (necrotizing fasciitis or myositis). We have adopted skin air sac as the route of bacterial infection for studying the role of SPE B in the mouse model of GAS infection. Previous studies in our laboratory indicated that these mutants caused less mortality and tissue damage than protease-positive strains. The role of SPE B was further confirmed by demonstrating that SPE B immunization of mice conferred protection from challenge with a lethal dose of protease-positive bacteria. To further explore the correlation of SPE B with the process of GAS diseases, the systemic effects by local infection were investigated in this study. We found that bacterial numbers in the exudates from the air pouches of mice infected with the wild-type strains were increased by the time, but not seen in mice infected with the speB mutants. The frequency of mice infected with the wild-type strains developed bacteremia was higher than that of mice infected with the speB mutants. Further, to observe whether the multiple organs were affected, the histopathologic changes of various organs were examined. We found severe tissue destruction in kidney and liver. Histopathologic changes in kidney and liver occurred at 24 h after bacteria inoculation, and the wild-type strains caused a higher severity compared to those of the speB mutants. The elevation of biochemical components (AST﹑ALT and BUN) levels in sera was correlated with liver and renal impairment, and the levels were higher in sera from mice infected with the wild-type strains than those from mice infected with the speB mutants. The histopathologic changes were not observed in brain and lung. The organ weights of spleen from mice infected with the wild-type strains were reduced at 48 h, but not seen in mice infected with the speB mutants. The increase of SPE B level in inoculation site and serum was detected with competition ELISA. In addition, the direct effects of SPE B in mice via intraperitoneal injection were studied using the recombinant wild-type SPE B and its mutant C192S. The results indicated that wild-type SPE B but not C192S caused local tissue damage and death in the animal. Taken together, a correlation of SPE B with bacteriologic and histopathologic changes is demonstrated in this study.