期刊
NATURE
卷 599, 期 7883, 页码 120-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41586-021-03986-2
关键词
-
资金
- EMBL
- JPIAMR grant
- ERC grant uCARE [819454]
- EMBL Interdisciplinary Postdoc programme under the Marie Sklodowska Curie Actions COFUND [291772, 664726]
- DFG (CMFI Cluster of Excellence) [EXC 2124]
- DFG (Emmy Noether Program)
- EMBO long-term postdoctoral fellowship
- Christiane Nusslein-Volhard-Stiftung
- JPIAMR grant EMBARK
- UK Medical Research Council [MC_UU_00025/11]
- DFG [CRC1371]
- ERC grant EVOGUTHEALTH [865615]
- DZIF
- CEGIMIR
- European Research Council (ERC) [865615, 819454] Funding Source: European Research Council (ERC)
The study categorized the activity spectra of antibiotics in gut bacteria, revealing distinct inhibition patterns of different antibiotic classes. The findings suggest potential strategies to protect beneficial bacteria by screening for drugs that counteract antibiotic activity.
Antibiotics are used to fight pathogens but also target commensal bacteria, disturbing the composition of gut microbiota and causing dysbiosis and disease(1). Despite this well-known collateral damage, the activity spectrum of different antibiotic classes on gut bacteria remains poorly characterized. Here we characterize further 144 antibiotics from a previous screen of more than 1,000 drugs on 38 representative human gut microbiome species(2). Antibiotic classes exhibited distinct inhibition spectra, including generation dependence for quinolones and phylogeny independence for beta-lactams. Macrolides and tetracyclines, both prototypic bacteriostatic protein synthesis inhibitors, inhibited nearly all commensals tested but also killed several species. Killed bacteria were more readily eliminated from in vitro communities than those inhibited. This species-specific killing activity challenges the long-standing distinction between bactericidal and bacteriostatic antibiotic classes and provides a possible explanation for the strong effect of macrolides on animal(3-5) and human(6,7) gut microbiomes. To mitigate this collateral damage of macrolides and tetracyclines, we screened for drugs that specifically antagonized the antibiotic activity against abundant Bacteroides species but not against relevant pathogens. Such antidotes selectively protected Bacteroides species from erythromycin treatment in human-stool-derived communities and gnotobiotic mice. These findings illluminate the activity spectra of antibiotics in commensal bacteria and suggest strategies to circumvent their adverse effects on the gut microbiota.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据