Dalesandro Brianna E, Pires Marcos M
Department of Chemistry, University of Virginia, Charlottesville, Virginia 22904, United States.
J Med Chem. 2023 Jan 12;66(1):503-515. doi: 10.1021/acs.jmedchem.2c01464. Epub 2022 Dec 23.
Immunological agents that supplement or modulate the host immune response have proven to have powerful therapeutic potential, although this modality is less explored against bacterial pathogens. We describe the application of a bacterial binding protein to re-engage the immune system toward pathogenic bacteria. More specifically, a hapten was conjugated to a protein expressed by ticks, called antifreeze glycoprotein (IAFGP), that has high affinity for the d-alanine residue on the bacterial peptidoglycan. We showed that a fragment of this protein retained high surface binding affinity. Moreover, conjugation of a hapten to this peptide led to the display of haptens on the cell surface of vancomycin-resistant . Hapten display then induced the recruitment of antibodies and promoted uptake of bacterial pathogens by immune cells. These results demonstrate the feasibility in using cell wall binding agents as the basis of a class of bacterial immunotherapies.
补充或调节宿主免疫反应的免疫制剂已被证明具有强大的治疗潜力,尽管这种方式针对细菌病原体的研究较少。我们描述了一种细菌结合蛋白在重新激发免疫系统对抗病原菌方面的应用。更具体地说,一种半抗原与蜱表达的一种蛋白质——抗冻糖蛋白(IAFGP)偶联,该蛋白对细菌肽聚糖上的D-丙氨酸残基具有高亲和力。我们发现该蛋白的一个片段保留了高表面结合亲和力。此外,将半抗原与该肽偶联导致在耐万古霉素菌的细胞表面展示半抗原。半抗原的展示随后诱导抗体募集并促进免疫细胞对细菌病原体的摄取。这些结果证明了使用细胞壁结合剂作为一类细菌免疫疗法基础的可行性。