title: Interaction between M-like protein and macrophage thioredoxin facilitates antiphagocytosis for Streptococcus equi ssp. zooepidemicus.
abstract: 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.
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Ma
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Junxi
authors.initials: J
authors.lastname: Zheng
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Yi
authors.forename: Hongjie
authors.initials: H
authors.lastname: Fan
authors.forename: Chengping
authors.initials: C
authors.lastname: Lu
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D016297:Mutagenesis, Site-Directed; D010100:Oxygen / Q000737:chemistry; D010587:Phagocytosis; D018502:Streptococcus equi / Q000378:metabolism*; D013552:Swine; D013879:Thioredoxins / Q000737:chemistry*; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000737:chemistry; D037521:Virulence Factors
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018076:DNA, Complementary; C107892:SzPSe protein, Streptococcus equi; D025801:Ubiquitin; D037521:Virulence Factors; D013879:Thioredoxins; D010100:Oxygen