Zurawski Daniel V, McLendon Molly K
Wound Infections Department, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Antibiotics (Basel). 2020 Apr 1;9(4):155. doi: 10.3390/antibiotics9040155.
In the beginning of the 21st century, the frequency of antimicrobial resistance (AMR) has reached an apex, where even 4th and 5th generation antibiotics are becoming useless in clinical settings. In turn, patients are suffering from once-curable infections, with increases in morbidity and mortality. The root cause of many of these infections are the ESKAPEE pathogens ( species, , , , , species, and ), which thrive in the nosocomial environment and are the bacterial species that have seen the largest rise in the acquisition of antibiotic resistance genes. While traditional small-molecule development still dominates the antibacterial landscape for solutions to AMR, some researchers are now turning to biological approaches as potential game changers. Monoclonal antibodies (mAbs)-more specifically, human monoclonal antibodies (Hu-mAbs)-have been highly pursued in the anti-cancer, autoimmune, and antiviral fields with many success stories, but antibody development for bacterial infection is still just scratching the surface. The untapped potential for Hu-mAbs to be used as a prophylactic or therapeutic treatment for bacterial infection is exciting, as these biologics do not have the same toxicity hurdles of small molecules, could have less resistance as they often target virulence proteins rather than proteins required for survival, and are narrow spectrum (targeting just one pathogenic species), therefore avoiding the disruption of the microbiome. This mini-review will highlight the current antibacterial mAbs approved for patient use, the success stories for mAb development, and new Hu-mAb products in the antibacterial pipeline.
在21世纪初，抗菌耐药性（AMR）的频率达到了顶点，在临床环境中，即使是第四代和第五代抗生素也变得无用。相应地，患者正遭受曾经可治愈的感染，发病率和死亡率不断上升。许多此类感染的根本原因是ESKAPEE病原体（粪肠球菌、屎肠球菌、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌和肠杆菌属），它们在医院环境中大量繁殖，是获得抗生素耐药基因增加最多的细菌种类。虽然传统的小分子开发在解决AMR的抗菌领域仍占主导地位，但一些研究人员现在正转向生物学方法，将其作为潜在的变革者。单克隆抗体（mAbs）——更具体地说，人源单克隆抗体（Hu-mAbs）——在抗癌、自身免疫和抗病毒领域受到高度追捧，并取得了许多成功案例，但针对细菌感染的抗体开发仍处于起步阶段。Hu-mAbs作为细菌感染的预防性或治疗性药物的未开发潜力令人兴奋，因为这些生物制剂没有小分子那样的毒性障碍，由于它们通常靶向毒力蛋白而非生存所需蛋白，可能产生的耐药性较低，并且具有窄谱性（仅针对一种致病物种），因此避免了对微生物群的破坏。本综述将重点介绍目前已批准用于患者的抗菌mAbs、mAb开发的成功案例以及抗菌领域正在研发的新型Hu-mAb产品。
