College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
PLoS One. 2012;7(2):e32099. doi: 10.1371/journal.pone.0032099. Epub 2012 Feb 27.
Streptococcus equi ssp. zooepidemicus (S. zooepidemicus, S.z) is one of the common pathogens that can cause septicemia, meningitis, and mammitis in domesticated species. M-like protein (SzP) is an important virulence factor of S. zooepidemicus and contributes to bacterial infection and antiphagocytosis. The interaction between SzP of S. zooepidemicus and porcine thioredoxin (TRX) was identified by the yeast two-hybrid and further confirmed by co-immunoprecipitation. SzP interacted with both reduced and the oxidized forms of TRX without inhibiting TRX activity. Membrane anchored SzP was able to recruit TRX to the surface, which would facilitate the antiphagocytosis of the bacteria. Further experiments revealed that TRX regulated the alternative complement pathway by inhibiting C3 convertase activity and associating with factor H (FH). TRX alone inhibited C3 cleavage and C3a production, and the inhibitory effect was additive when FH was also present. TRX inhibited C3 deposition on the bacterial surface when it was recruited by SzP. These new findings indicated that S. zooepidemicus used SzP to recruit TRX and regulated the alternative complement pathways to evade the host immune phagocytosis.
马链球菌兽疫亚种（S. zooepidemicus，S.z）是一种常见的病原体，可引起家畜的败血症、脑膜炎和乳腺炎。M 样蛋白（SzP）是马链球菌兽疫亚种的重要毒力因子，有助于细菌感染和抗吞噬作用。通过酵母双杂交实验鉴定出马链球菌兽疫亚种 SzP 与猪硫氧还蛋白（TRX）的相互作用，并用共免疫沉淀进一步证实。SzP 与还原和氧化形式的 TRX 相互作用而不抑制 TRX 活性。膜锚定的 SzP 能够将 TRX 募集到细菌表面，这有助于细菌的抗吞噬作用。进一步的实验表明，TRX 通过抑制 C3 转化酶的活性和与因子 H（FH）结合来调节替代补体途径。TRX 单独抑制 C3 切割和 C3a 的产生，当 FH 也存在时，这种抑制作用具有加性。当 SzP 募集 TRX 时，TRX 抑制 C3 在细菌表面的沉积。这些新发现表明，马链球菌兽疫亚种利用 SzP 招募 TRX，并调节替代补体途径来逃避宿主免疫吞噬。
