Bergmann Simone, Eichhorn Inga, Kohler Thomas P, Hammerschmidt Sven, Goldmann Oliver, Rohde Manfred, Fulde Marcus
Department of Medical Microbiology, Helmholtz Center for Infection Research Braunschweig, Germany.
Institute of Microbiology and Epizootics, Centre for Infection Medicine, Freie Universität Berlin Berlin, Germany.
Front Cell Infect Microbiol. 2017 Mar 28;7:80. doi: 10.3389/fcimb.2017.00080. eCollection 2017.
The M protein of (SCM) is a virulence factor and serves as a surface-associated receptor with a particular affinity for mini-plasminogen, a cleavage product of the broad-spectrum serine protease plasmin. Here, we report that SCM has an additional high-affinity immunoglobulin G (IgG) binding activity. The ability of a particular isolate to bind to IgG significantly correlates with a -positive phenotype, suggesting a dominant role of SCM as an IgG receptor. Subsequent heterologous expression of SCM in non-IgG binding and Western Blot analysis with purified recombinant SCM proteins confirmed its IgG receptor function. As expected for a zoonotic agent, the SCM-IgG interaction is species-unspecific, with a particular affinity of SCM for IgGs derived from human, cats, dogs, horses, mice, and rabbits, but not from cows and goats. Similar to other streptococcal IgG-binding proteins, the interaction between SCM and IgG occurs via the conserved Fc domain and is, therefore, non-opsonic. Interestingly, the interaction between SCM and IgG-Fc on the bacterial surface specifically prevents opsonization by C1q, which might constitute another anti-phagocytic mechanism of SCM. Extensive binding analyses with a variety of different truncated SCM fragments defined a region of 52 amino acids located in the central part of the mature SCM protein which is important for IgG binding. This binding region is highly conserved among SCM proteins derived from different isolates but differs significantly from IgG-Fc receptors of and sub. , respectively. In summary, we present an additional role of SCM in the pathogen-host interaction of . The detailed analysis of the SCM-IgG interaction should contribute to a better understanding of the complex roles of M proteins in streptococcal pathogenesis.
猪链球菌（SCM）的M蛋白是一种毒力因子，作为一种表面相关受体，对广谱丝氨酸蛋白酶纤溶酶的裂解产物微型纤溶酶原具有特殊亲和力。在此，我们报告SCM具有额外的高亲和力免疫球蛋白G（IgG）结合活性。特定猪链球菌分离株与IgG结合的能力与M蛋白阳性表型显著相关，表明SCM作为IgG受体起主要作用。随后在不结合IgG的菌株中对SCM进行异源表达，并使用纯化的重组SCM蛋白进行蛋白质免疫印迹分析，证实了其IgG受体功能。正如人畜共患病原体所预期的那样，SCM与IgG的相互作用具有物种非特异性，SCM对源自人类、猫、狗、马、小鼠和兔子的IgG具有特殊亲和力，但对牛和山羊的IgG没有亲和力。与其他链球菌IgG结合蛋白类似，SCM与IgG之间的相互作用通过保守的Fc结构域发生，因此是非调理素性的。有趣的是，细菌表面的SCM与IgG-Fc之间的相互作用特异性地阻止了C1q的调理作用，这可能构成SCM的另一种抗吞噬机制。对各种不同截短的SCM片段进行广泛的结合分析，确定了位于成熟SCM蛋白中部的一个52个氨基酸的区域，该区域对IgG结合很重要。该结合区域在源自不同猪链球菌分离株的SCM蛋白中高度保守，但分别与化脓性链球菌和无乳链球菌的IgG-Fc受体有显著差异。总之，我们展示了SCM在猪链球菌病原体-宿主相互作用中的另一个作用。对SCM-IgG相互作用的详细分析应有助于更好地理解M蛋白在链球菌发病机制中的复杂作用。
