Antibacterial Discovery Performance Unit, GlaxoSmithKline, Collegeville, PA 19426.
Research & Development Centre, GlaxoSmithKline, 53100 Siena, Italy
Proc Natl Acad Sci U S A. 2018 Dec 18;115(51):12887-12895. doi: 10.1073/pnas.1717160115.
Bacterial infections have been traditionally controlled by antibiotics and vaccines, and these approaches have greatly improved health and longevity. However, multiple stakeholders are declaring that the lack of new interventions is putting our ability to prevent and treat bacterial infections at risk. Vaccine and antibiotic approaches still have the potential to address this threat. Innovative vaccine technologies, such as reverse vaccinology, novel adjuvants, and rationally designed bacterial outer membrane vesicles, together with progress in polysaccharide conjugation and antigen design, have the potential to boost the development of vaccines targeting several classes of multidrug-resistant bacteria. Furthermore, new approaches to deliver small-molecule antibacterials into bacteria, such as hijacking active uptake pathways and potentiator approaches, along with a focus on alternative modalities, such as targeting host factors, blocking bacterial virulence factors, monoclonal antibodies, and microbiome interventions, all have potential. Both vaccines and antibacterial approaches are needed to tackle the global challenge of antimicrobial resistance (AMR), and both areas have the underpinning science to address this need. However, a concerted research agenda and rethinking of the value society puts on interventions that save lives, by preventing or treating life-threatening bacterial infections, are needed to bring these ideas to fruition.
细菌感染传统上通过抗生素和疫苗来控制，这些方法极大地提高了健康水平和延长了寿命。然而，多方利益相关者表示，缺乏新的干预措施使我们预防和治疗细菌感染的能力面临风险。疫苗和抗生素方法仍然有潜力应对这一威胁。创新的疫苗技术，如反向疫苗学、新型佐剂和经过合理设计的细菌外膜囊泡，以及多糖缀合和抗原设计方面的进展，有可能促进针对几类多药耐药菌的疫苗的开发。此外，将小分子抗菌药物递送到细菌中的新方法，如劫持主动摄取途径和增效剂方法，以及关注替代方式，如针对宿主因素、阻断细菌毒力因子、单克隆抗体和微生物组干预等，都具有潜力。疫苗和抗菌方法都需要应对全球抗菌药物耐药性（AMR）挑战，这两个领域都有解决这一需求的基础科学。然而，需要制定协调一致的研究议程，并重新思考社会对挽救生命的干预措施（通过预防或治疗危及生命的细菌感染）的重视程度，才能将这些想法变为现实。
