Dalesandro Brianna E, Pires Marcos M
Department of Chemistry, University of Virginia, Charlottesville, Virginia 22904, United States.
ACS Infect Dis. 2021 May 14;7(5):1116-1125. doi: 10.1021/acsinfecdis.0c00547. Epub 2020 Nov 12.
For the foreseeable future, conventional small molecule antibiotics will continue to be the predominant treatment option due to wide patient coverage and low costs. Today, however, there is already a significant portion of patients that fail to respond to small molecule antibiotics and, according to the Centers for Disease Control and Prevention, this number is poised to increase in the coming years. Therefore, this rise in drug resistant bacteria must be countered with the development of nontraditional therapies. We propose a measure based on the re-engagement of the immune system toward pathogenic bacteria by grafting bacterial cell surfaces with immunogenic agents. Herein, we describe a class of cell wall analogues that selectively graft bacterial cell surfaces with epitopes that promote their opsonization. More specifically, synthetic analogues of peptidoglycan conjugated to haptens were designed to be incorporated by the cell wall biosynthetic machinery into live . is a formidable human pathogen that poses a considerable burden to healthcare and often results in fatalities. We showed that treatment of and vancomycin-resistant strains with the cell wall analogues led to the display of haptens on the cell surface, which induced the recruitment of antibodies existing in the serum of humans. These results demonstrate the feasibility in using cell wall analogues as the basis of a class of bacterial immunotherapies against dangerous pathogens.
在可预见的未来,由于患者覆盖面广且成本低,传统小分子抗生素仍将是主要的治疗选择。然而,如今已有相当一部分患者对小分子抗生素无反应,且据疾病控制与预防中心称,这一数字在未来几年还会上升。因此,必须通过开发非传统疗法来应对耐药细菌的增加。我们提出一项基于通过用免疫原性试剂嫁接细菌细胞表面,使免疫系统重新针对病原菌的措施。在此,我们描述了一类细胞壁类似物,它们能选择性地将促进其调理作用的表位嫁接至细菌细胞表面。更具体地说,与半抗原缀合的肽聚糖合成类似物经设计,可被细胞壁生物合成机制整合到活的……中。……是一种强大的人类病原体,给医疗保健带来相当大的负担,且常导致死亡。我们表明,用细胞壁类似物处理……和耐万古霉素菌株会导致半抗原在细胞表面展示,从而诱导人体血清中现有抗体的募集。这些结果证明了使用细胞壁类似物作为一类针对危险病原体的细菌免疫疗法基础的可行性。