Kunitomo Eiji, Terao Yutaka, Okamoto Shigefumi, Rikimaru Tetsuya, Hamada Shigeyuki, Kawabata Shigetada
Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565-0871, Japan.
Microbes Infect. 2008 Apr;10(4):414-23. doi: 10.1016/j.micinf.2008.01.003. Epub 2008 Jan 12.
Four Streptococcus pneumoniae genes, phtA, phtB, phtD, and phtE, as well as the slr gene of group A streptococci (GAS), encode proteins with a histidine triad motif (HxxHxH). Pht proteins function as protective antigens against S. pneumoniae infection. A search of the GAS genome database identified a novel protein, HtpA, possessing five histidine triad motifs. The htpA gene was shown to encode a 92.5-kDa protein located downstream of the fbaA and lbp genes, while Western blot analyses revealed that HtpA protein was expressed on the cell surfaces of all group A, B, C, and G streptococcal isolates tested. Immunization of mice with rHtpA induced antigen-specific antibody production and was effective after a single immunization, with antibody titers remaining constant for at least 84days. In addition, HtpA-immunized mice survived after challenge with GAS strains isolated from patients with streptococcal toxic shock syndrome for significantly longer periods than sham-immunized mice. In that experiment, the HtpA-specific antibody was effectively induced by a single immunization and the specific antibody titer remained constant for at least 84days. These results indicate that the novel histidine triad protein HtpA is a candidate vaccine for GAS infection.
肺炎链球菌的四个基因phtA、phtB、phtD和phtE，以及A组链球菌（GAS）的slr基因，编码具有组氨酸三联体基序（HxxHxH）的蛋白质。Pht蛋白作为抗肺炎链球菌感染的保护性抗原发挥作用。对GAS基因组数据库的搜索鉴定出一种具有五个组氨酸三联体基序的新型蛋白质HtpA。htpA基因被证明编码一种位于fbaA和lbp基因下游的92.5 kDa蛋白质，而蛋白质印迹分析显示，HtpA蛋白在所有测试的A、B、C和G组链球菌分离株的细胞表面表达。用重组HtpA免疫小鼠可诱导抗原特异性抗体产生，单次免疫后即有效，抗体滴度至少84天保持恒定。此外，用HtpA免疫的小鼠在受到从链球菌中毒性休克综合征患者分离的GAS菌株攻击后存活的时间明显长于假免疫小鼠。在该实验中，单次免疫可有效诱导HtpA特异性抗体，且特异性抗体滴度至少84天保持恒定。这些结果表明，新型组氨酸三联体蛋白HtpA是GAS感染的候选疫苗。
