Intrahospital Infections Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Spain.
Front Immunol. 2019 Dec 10;10:2841. doi: 10.3389/fimmu.2019.02841. eCollection 2019.
Over the past few decades, antimicrobial resistance has emerged as an important threat to public health due to the global dissemination of multidrug-resistant strains from several bacterial species. This worrisome trend, in addition to the paucity of new antibiotics with novel mechanisms of action in the development pipeline, warrants the development of non-antimicrobial approaches to combating infection caused by these isolates. Monoclonal antibodies (mAbs) have emerged as highly effective molecules for the treatment of multiple diseases. However, in spite of the fact that antibodies play an important role in protective immunity against bacteria, only three mAb therapies have been approved for clinical use in the treatment of bacterial infections. In the present review, we briefly outline the therapeutic potential of mAbs in the treatment of bacterial diseases and discuss how their development can be facilitated when assisted by "omics" technologies and interpreted under a systems biology paradigm. Specifically, methods employing large genomic, transcriptomic, structural, and proteomic datasets allow for the rational identification of epitopes. Ideally, these include those that are present in the majority of circulating isolates, highly conserved at the amino acid level, surface-exposed, located on antigens essential for virulence, and expressed during critical stages of infection. Therefore, these knowledge-based approaches can contribute to the identification of high-value epitopes for the development of effective mAbs against challenging bacterial clones.
在过去的几十年中，由于多种耐药菌株在全球范围内的传播，抗菌药物耐药性已成为公共卫生的一个重要威胁。这种令人担忧的趋势，加上新的抗生素在开发渠道中缺乏具有新颖作用机制的抗生素，因此需要开发非抗菌方法来对抗这些分离物引起的感染。单克隆抗体 (mAb) 已成为治疗多种疾病的有效分子。然而，尽管抗体在针对细菌的保护性免疫中发挥着重要作用，但只有三种 mAb 疗法被批准用于临床治疗细菌感染。在本综述中，我们简要概述了 mAb 在治疗细菌病方面的治疗潜力，并讨论了在“组学”技术的辅助下，如何在系统生物学范例下促进其发展。具体来说，使用大型基因组、转录组、结构和蛋白质组数据集的方法可以合理地识别表位。理想情况下，这些表位包括存在于大多数循环分离物中的表位、在氨基酸水平上高度保守的表位、表面暴露的表位、位于对毒力至关重要的抗原上的表位，以及在感染的关键阶段表达的表位。因此，这些基于知识的方法有助于识别针对挑战性细菌克隆开发有效 mAb 的高价值表位。
