宿主-病原体相互作用的药理学靶向：对抗耐药超级细菌的传统抗生素替代方案
Pharmacological Targeting of the Host-Pathogen Interaction: Alternatives to Classical Antibiotics to Combat Drug-Resistant Superbugs.
作者信息
Munguia Jason, Nizet Victor
机构信息
Department of Pediatrics, Division of Host-Microbe Systems and Therapeutics, University of California San Diego, La Jolla, CA 92093, USA; Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA 92093, USA.
Department of Pediatrics, Division of Host-Microbe Systems and Therapeutics, University of California San Diego, La Jolla, CA 92093, USA; Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA 92093, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA; Rady Children's Hospital, San Diego, CA 92123, USA.
出版信息
Trends Pharmacol Sci. 2017 May;38(5):473-488. doi: 10.1016/j.tips.2017.02.003. Epub 2017 Mar 8.
The rise of multidrug-resistant pathogens and the dearth of new antibiotic development place an existential strain on successful infectious disease therapy. Breakthrough strategies that go beyond classical antibiotic mechanisms are needed to combat this looming public health catastrophe. Reconceptualizing antibiotic therapy in the richer context of the host-pathogen interaction is required for innovative solutions. By defining specific virulence factors, the essence of a pathogen, and pharmacologically neutralizing their activities, one can block disease progression and sensitize microbes to immune clearance. Likewise, host-directed strategies to boost phagocyte bactericidal activity, enhance leukocyte recruitment, or reverse pathogen-induced immunosuppression seek to replicate the success of cancer immunotherapy in the field of infectious diseases. The answer to the threat of multidrug-resistant pathogens lies 'outside the box' of current antibiotic paradigms.
多重耐药病原体的出现以及新抗生素研发的匮乏给成功的传染病治疗带来了生存压力。需要超越传统抗生素作用机制的突破性策略来应对这一迫在眉睫的公共卫生灾难。为了找到创新解决方案，需要在宿主与病原体相互作用这一更丰富的背景下重新构想抗生素治疗。通过定义特定的毒力因子、病原体的本质，并通过药理学方法中和其活性，可以阻断疾病进展并使微生物对免疫清除敏感。同样，旨在增强吞噬细胞杀菌活性、促进白细胞募集或逆转病原体诱导的免疫抑制的宿主导向策略，试图在传染病领域复制癌症免疫疗法的成功。应对多重耐药病原体威胁的答案在于当前抗生素范式的“框框”之外。
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