Active and passive immunizations with the streptococcal esterase Sse protect mice against subcutaneous infection with group A Streptococci
Active and passive immunizations with the streptococcal esterase Sse protect mice against subcutaneous infection with group A Streptococci
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DOI：
10.1128/iai.00038-07
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发表时间：
2007-07-01
影响因子：
3.1
通讯作者：
Lei, Benfang
中科院分区：
文献类型：
--
作者：
Liu, Mengyao;Zhu, Hui;Lei, Benfang
人类病原体A组链球菌(GAS)产生许多在GAS发病机制中发挥重要作用的分泌性蛋白，包括降解蛋白质和核酸的水解酶。本研究针对的是另一种水解酶--羧酸酯酶，目的是鉴定GAS酯酶，并确定它是否是保护性抗原。克隆了可能的酯酶基因SPy1718，制备了重组蛋白(SSE)。在GAS培养上清液中检测到SSE，链球菌性咽炎患者血清转化为SSE，表明SSE在体内和体外都能产生。SSE水解对硝基苯丁酸酯，残基(178)Ser是该酯酶活性的关键。根据现有的基因组数据库，存在两个SSE变异体复合体，与先前发现的两个抗原性SSE变异体一致。复合体I包括血清型M1、M2、M3、M5、M6、M12和M18，而M4、M28和M49属于复合体II。SSE变异体在每个复合体内的氨基酸序列有98%的同源性，但两组之间的差异约为37%。M1 SSE主动免疫可显著保护小鼠免受致死性M1和M3毒株的皮下感染，并抑制小鼠皮肤组织的气体侵袭。用抗SSE抗血清被动免疫也能显著保护小鼠免受皮下气体感染，表明这种保护作用是由SSE特异性抗体介导的。结果表明，SSE在组织侵袭中起重要作用，是一种对多种血清型的GAS皮下感染具有保护作用的抗原。
The human pathogen group A Streptococcus (GAS) produces many secreted proteins that play important roles in GAS pathogenesis, including hydrolases that degrade proteins and nucleic acids. This study targets another kind of hydrolase, carboxylic esterase, with the objectives of identifying GAS esterase and determining whether it is a protective antigen. The putative esterase gene SPy1718 was cloned, and the recombinant protein (Sse) was prepared. Sse was detected in GAS culture supernatant, and patients with streptococcal pharyngitis seroconverted to Sse, indicating that Sse was produced in vivo and in vitro. Sse hydrolyzes p-nitrophenyl butyrate, and the residue (178)Ser is critical for this esterase activity. There are two Sse variant complexes according to the available genome databases, consistent with the previous finding of two antigenic Sse variants. Complex I includes serotypes M1, M2, M3, M5, M6, M12, and M18, whereas M4, M28, and M49 belong to complex II. Sse variants share > 98% identity in amino acid sequence within each complex but have about 37% variation between the two groups. Active immunization with M1 Sse significantly protects mice against lethal subcutaneous infection with virulent M1 and M3 strains and inhibits GAS invasion of mouse skin tissue. Passive immunization with anti-Sse antiserum also significantly protects mice against subcutaneous GAS infection, indicating that the protection is mediated by Sse-specific antibodies. The results suggest that Sse plays an important role in tissue invasion and is an antigen protective in subcutaneous infection against GAS strains of more than one serotype.