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DOI | 10.1038/s41559-021-01511-2 |
Bottleneck size and selection level reproducibly impact evolution of antibiotic resistance | |
Mahrt N.; Tietze A.; Künzel S.; Franzenburg S.; Barbosa C.; Jansen G.; Schulenburg H. | |
发表日期 | 2021 |
ISSN | 2397-334X |
起始页码 | 1233 |
结束页码 | 1242 |
卷号 | 5期号:9 |
英文摘要 | During antibiotic treatment, the evolution of bacterial pathogens is fundamentally affected by bottlenecks and varying selection levels imposed by the drugs. Bottlenecks—that is, reductions in bacterial population size—lead to an increased influence of random effects (genetic drift) during bacterial evolution, and varying antibiotic concentrations during treatment may favour distinct resistance variants. Both aspects influence the process of bacterial evolution during antibiotic therapy and thereby treatment outcome. Surprisingly, the joint influence of these interconnected factors on the evolution of antibiotic resistance remains largely unexplored. Here we combine evolution experiments with genomic and genetic analyses to demonstrate that bottleneck size and antibiotic-induced selection reproducibly impact the evolutionary path to resistance in pathogenic Pseudomonas aeruginosa, one of the most problematic opportunistic human pathogens. Resistance is favoured—expectedly—under high antibiotic selection and weak bottlenecks, but—unexpectedly—also under low antibiotic selection and severe bottlenecks. The latter is likely to result from a reduced probability of losing favourable variants through drift under weak selection. Moreover, the absence of high resistance under low selection and weak bottlenecks is caused by the spread of low-resistance variants with high competitive fitness under these conditions. We conclude that bottlenecks, in combination with drug-induced selection, are currently neglected key determinants of pathogen evolution and outcome of antibiotic treatment. ? 2021, The Author(s). |
语种 | 英语 |
scopus关键词 | antiinfective agent; antibiotic resistance; bacterium; genetics; human; Pseudomonas aeruginosa; Anti-Bacterial Agents; Bacteria; Drug Resistance, Microbial; Humans; Pseudomonas aeruginosa |
来源期刊 | Nature Ecology & Evolution
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文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/256864 |
作者单位 | Evolutionary Ecology and Genetics, Department of Zoology, Christian-Albrechts-University of Kiel, Kiel, Germany; Department of Evolutionary Genetics, Max-Planck-Institute for Evolutionary Biology, Pl?n, Germany; Genetics and Bioinformatics, Department of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany; Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States; Antibiotic Resistance Group, Max-Planck-Institute for Evolutionary Biology, Pl?n, Germany |
推荐引用方式 GB/T 7714 | Mahrt N.,Tietze A.,Künzel S.,et al. Bottleneck size and selection level reproducibly impact evolution of antibiotic resistance[J],2021,5(9). |
APA | Mahrt N..,Tietze A..,Künzel S..,Franzenburg S..,Barbosa C..,...&Schulenburg H..(2021).Bottleneck size and selection level reproducibly impact evolution of antibiotic resistance.Nature Ecology & Evolution,5(9). |
MLA | Mahrt N.,et al."Bottleneck size and selection level reproducibly impact evolution of antibiotic resistance".Nature Ecology & Evolution 5.9(2021). |
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