The Search for 'Evolution-Proof' Antibiotics

doi:10.1016/j.tim.2017.11.005

2018-06-01

Graham Bell *

R. Craig MacLean

DOI：10.1016/j.tim.2017.11.005

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摘要

En 中文

The effectiveness of antibiotics has been widely compromised by the evolution of resistance among pathogenic bacteria. It would be restored by the development of antibiotics to which bacteria cannot evolve resistance. We first discuss two kinds of 'evolution-proof' antibiotic. The first comprises literally evolution-proof antibiotics to which bacteria cannot become resistant by mutation or horizontal gene transfer. The second category comprises agents to which resistance may arise, but so rarely that it does not become epidemic. The likelihood that resistance to a novel agent will spread is evaluated here by a simple model that includes biological and therapeutic parameters governing the evolution of resistance within hosts and the transmission of resistant strains between hosts. This model leads to the conclusion that epidemic spread is unlikely if the frequency of mutations that confer resistance falls below a defined minimum value, and it identifies potential targets for intervention to prevent the evolution of resistance. Whether or not evolution-proof antibiotics are ever found, searching for them is likely to improve the deployment of new and existing agents by advancing our understanding of how resistance evolves.

Keyword:

RESISTANT STAPHYLOCOCCUS-AUREUS

ANTIMICROBIAL PEPTIDES

MYCOBACTERIUM-TUBERCULOSIS

BACTERIAL-RESISTANCE

SPONTANEOUS MUTATION

INFECTIOUS-DISEASES

SELECTION

COST

MECHANISMS

EMERGENCE

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期刊

Trends in Microbiology

IF:

14.9

论文数:

3.9K

被引数:

1.9W

机构

university of oxford

学者数:

9.8W

论文数: 8.6W

被引数: 137

McGill University

学者数:

5.5W

论文数: 4.9W

被引数: 7.0W

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