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整合子活性加速了抗生素耐药性的进化。

Integron activity accelerates the evolution of antibiotic resistance.

机构信息

University of Oxford, Department of Zoology, Oxford, United Kingdom.

Universidad Complutense de Madrid, Departamento de Sanidad Animal and VISAVET, Madrid, Spain.

出版信息

Elife. 2021 Feb 26;10:e62474. doi: 10.7554/eLife.62474.

DOI:10.7554/eLife.62474
PMID:33634790
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8024014/
Abstract

Mobile integrons are widespread genetic platforms that allow bacteria to modulate the expression of antibiotic resistance cassettes by shuffling their position from a common promoter. Antibiotic stress induces the expression of an integrase that excises and integrates cassettes, and this unique recombination and expression system is thought to allow bacteria to 'evolve on demand' in response to antibiotic pressure. To test this hypothesis, we inserted a custom three-cassette integron into and used experimental evolution to measure the impact of integrase activity on adaptation to gentamicin. Crucially, integrase activity accelerated evolution by increasing the expression of a gentamicin resistance cassette through duplications and by eliminating redundant cassettes. Importantly, we found no evidence of deleterious off-target effects of integrase activity. In summary, integrons accelerate resistance evolution by rapidly generating combinatorial variation in cassette composition while maintaining genomic integrity.

摘要

移动整合子是广泛存在的遗传平台，使细菌能够通过从共同启动子 shuffling 它们的位置来调节抗生素抗性盒的表达。抗生素应激诱导整合酶的表达，该酶切除并整合盒，这种独特的重组和表达系统被认为允许细菌在抗生素压力下“按需进化”。为了验证这一假说，我们将一个定制的三盒整合子插入到基因组中，并通过实验进化来测量整合酶活性对庆大霉素适应的影响。至关重要的是，整合酶活性通过重复和消除冗余盒来增加庆大霉素抗性盒的表达，从而加速了进化。重要的是，我们没有发现整合酶活性的有害脱靶效应的证据。总之，整合子通过快速产生盒组成的组合变异，同时保持基因组完整性，加速了耐药性的进化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5fe/8024014/0057e6c4393c/elife-62474-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5fe/8024014/26174f3938b8/elife-62474-fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5fe/8024014/8ee273d748bc/elife-62474-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5fe/8024014/878959d385fd/elife-62474-fig3-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5fe/8024014/b224859a9771/elife-62474-fig3-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5fe/8024014/88186b997dac/elife-62474-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5fe/8024014/65750825c31d/elife-62474-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5fe/8024014/cbda7d98c291/elife-62474-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5fe/8024014/098aa76d3ab3/elife-62474-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5fe/8024014/0057e6c4393c/elife-62474-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5fe/8024014/26174f3938b8/elife-62474-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5fe/8024014/7d8960b8d97e/elife-62474-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5fe/8024014/6a5eaf2ce9fc/elife-62474-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5fe/8024014/ded260d3ea99/elife-62474-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5fe/8024014/8ee273d748bc/elife-62474-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5fe/8024014/878959d385fd/elife-62474-fig3-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5fe/8024014/b224859a9771/elife-62474-fig3-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5fe/8024014/88186b997dac/elife-62474-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5fe/8024014/65750825c31d/elife-62474-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5fe/8024014/cbda7d98c291/elife-62474-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5fe/8024014/098aa76d3ab3/elife-62474-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5fe/8024014/0057e6c4393c/elife-62474-fig6.jpg

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