Filik-Matyjaszczyk Karolina, Matyjaszczyk Irwin, Ciesielska Marzena, Szermer-Olearnik Bożena, Mikołajczyk Krzysztof, Gamian Andrzej
Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114, Wroclaw, Poland.
Department of Biochemistry, Selvita S.A, 30-394, Cracow, Poland.
AMB Express. 2025 Sep 26;15(1):135. doi: 10.1186/s13568-025-01948-9.
Bacteriophage receptor binding proteins (RBPs) belong to a group of proteins that are components of the bacteriophage tail. RBPs are mainly responsible for recognizing receptors on the bacterial host surface and enabling infection and subsequent progeny phage multiplication. Our previous research suggested that recombinant tail fiber gp17 (TFPgp17) protein from Yersinia enterocolitica phage φYeO3-12 recognizes serotype O:3 with high specificity and could be used as a diagnostic tool. In this paper, we study the possibility of using modified TFPgp17 in fusion with IgG1 Fc immunoglobulin fragment (Fc_TFPgp17) to improve the efficacy of pathogen recognition by phagocytic cells, opsonization of bacterial cells, and then phagocytosis by the THP-1 macrophages and the HL-60 neutrophils. We demonstrate that the Fc_TFPgp17 protein can bind both bacterial and phagocytic cells, due to the presence of the RBP domain and the IgG1 Fc fragment, respectively. Additionally, it contributes to the better recognition of bacterial cells and their subsequent phagocytosis by phagocytes. Additionally, we proved that glycosylation of Fc_TFPgp17 which occurred during protein production, harms the ability to recognize Y. enterocolitica O:3. Fc_TFPgp17 is a bispecific protein that possesses two biological functions: (I) recognized Y. enterocolitica O:3 cells via phage RBP (TFPgp17) and (II) recognized phagocytic cells via Fc-fragment IgG1 immunoglobulin. In this work, we demonstrated that the recombined bispecific protein facilitates more effective recognition and opsonization of the pathogenic bacterial cell, leading to its subsequent phagocytosis.
噬菌体受体结合蛋白(RBPs)属于构成噬菌体尾部的一组蛋白质。RBPs主要负责识别细菌宿主表面的受体,并促成感染及随后子代噬菌体的增殖。我们之前的研究表明,来自小肠结肠炎耶尔森菌噬菌体φYeO3 - 12的重组尾丝gp17(TFPgp17)蛋白能高度特异性地识别O:3血清型,可作为一种诊断工具。在本文中,我们研究了将修饰后的TFPgp17与IgG1 Fc免疫球蛋白片段融合(Fc_TFPgp17),以提高吞噬细胞识别病原体、调理细菌细胞以及随后THP - 1巨噬细胞和HL - 60中性粒细胞吞噬作用的效果的可能性。我们证明,由于分别存在RBP结构域和IgG1 Fc片段,Fc_TFPgp17蛋白既能结合细菌细胞,也能结合吞噬细胞。此外,它有助于更好地识别细菌细胞以及随后吞噬细胞对其的吞噬作用。此外,我们证明了蛋白质生产过程中发生的Fc_TFPgp17糖基化损害了其识别小肠结肠炎耶尔森菌O:3的能力。Fc_TFPgp17是一种双特异性蛋白,具有两种生物学功能:(I)通过噬菌体RBP(TFPgp17)识别小肠结肠炎耶尔森菌O:3细胞,(II)通过Fc片段IgG1免疫球蛋白识别吞噬细胞。在这项工作中,我们证明了重组双特异性蛋白促进了对病原菌细胞更有效的识别和调理作用,导致其随后被吞噬。