Antibiotics that affect translation can antagonize phage infectivity by interfering with the deployment of counter-defenses.
Antibiotics that affect translation can antagonize phage infectivity by interfering with the deployment of counter-defenses.
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DOI：
10.1073/pnas.2216084120
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发表时间：
2023-01-24
影响因子：
11.1
通讯作者：
van Houte, Stineke
中科院分区：
文献类型：
--
作者：
Pons, Benoit J.;Dimitriu, Tatiana;Westra, Edze R.;van Houte, Stineke
由于目前的抗生素危机，人们对噬菌体-抗生素联合疗法的兴趣越来越大。我们的结果有助于理解抗生素-噬菌体的协同和拮抗作用如何依赖于定义噬菌体感染性和宿主免疫的分子相互作用。噬菌体被认为在形成微生物区系和诱导生态失调方面发挥着重要作用。因此，深入了解抗生素对噬菌体-细菌相互作用的影响对动物和人类的健康具有重要的应用意义。越来越清楚的是，抗生素可以对噬菌体(噬菌体)的感染性产生积极和消极的影响，但潜在的机制往往尚不清楚。在这里，我们证明了针对蛋白质翻译机制的抗生素可以通过干扰噬菌体编码的反防御蛋白的产生从根本上改变细菌-噬菌体相互作用的结果。具体地说，以铜绿假单胞菌PA14和噬菌体DMS3vir为模型，我们表明，当环境中存在翻译抑制剂时，具有集群规则间隔短回文重复的细菌免疫系统(CRISPR-Cas)对编码抗CRISPR(ACR)基因的噬菌体的免疫水平有所提高。CRISPR-CA是非常流行的防御系统，使细菌能够以序列特异的方式检测和破坏噬菌体基因组。作为回应，许多噬菌体编码ACR基因，这些基因在感染后立即表达，以抑制CRISPR-Cas免疫反应的关键步骤。我们的数据表明，虽然携带ACR基因的噬菌体可以在没有抗生素的情况下在具有CRISPR-Cas免疫系统的细菌上有效地扩增，但作用于蛋白质翻译的抗生素的存在阻止了噬菌体的放大，同时保护细菌免受裂解。
Due to the current antibiotic crisis, there is a rising interest in combined phage-antibiotics therapy. Our results help to understand how antibiotics-phage synergy and antagonism depend on the molecular interactions that define phage infectivity and host immunity. Phages are thought to play a prominent role in shaping microbiota and inducing dysbiosis. Hence, insights on how antibiotics impact phage–bacteria interactions are of applied significance for animal and human health. It is becoming increasingly clear that antibiotics can both positively and negatively impact the infectivity of bacteriophages (phage), but the underlying mechanisms often remain unclear. Here we demonstrate that antibiotics that target the protein translation machinery can fundamentally alter the outcome of bacteria–phage interactions by interfering with the production of phage-encoded counter-defense proteins. Specifically, using Pseudomonas aeruginosa PA14 and phage DMS3vir as a model, we show that bacteria with Clustered Regularly Interspaced Short Palindromic Repeat, CRISPR associated (CRISPR-Cas) immune systems have elevated levels of immunity against phage that encode anti-CRISPR (acr) genes when translation inhibitors are present in the environment. CRISPR-Cas are highly prevalent defense systems that enable bacteria to detect and destroy phage genomes in a sequence-specific manner. In response, many phages encode acr genes that are expressed immediately following the infection to inhibit key steps of the CRISPR-Cas immune response. Our data show that while phage-carrying acr genes can amplify efficiently on bacteria with CRISPR-Cas immune systems in the absence of antibiotics, the presence of antibiotics that act on protein translation prevents phage amplification, while protecting bacteria from lysis.
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影响因子：
14.9
作者：
Birkholz, Nils;Fagerlund, Robert D.;Fineran, Peter C.
通讯作者：
Fineran, Peter C.
影响因子：
5.4
作者：
Ceyssens, Pieter-Jan;Minakhin, Leonid;Lavigne, Rob
通讯作者：
Lavigne, Rob
影响因子：
30.3
作者：
Dimitriu, Tatiana;Kurilovich, Elena;Westra, Edze R.
通讯作者：
Westra, Edze R.
DOI：
10.3390/ph14111162
发表时间：
2021-11-15
期刊：
Pharmaceuticals (Basel, Switzerland)
影响因子：
--
作者：
Danis-Wlodarczyk KM;Cai A;Chen A;Gittrich MR;Sullivan MB;Wozniak DJ;Abedon ST
通讯作者：
Abedon ST
影响因子：
4.8
作者：
Akturk, Ergun;Oliveira, Hugo;Azeredo, Joana
通讯作者：
Azeredo, Joana