Cazares Daniel, Cazares Adrian, Figueroa Wendy, Guarneros Gabriel, Edwards Robert A, Vinuesa Pablo
Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico
EMBL's European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge, United Kingdom.
mSystems. 2021 Feb 2;6(1):e00773-20. doi: 10.1128/mSystems.00773-20.
Phages are generally described as species specific or even strain specific, implying an inherent limitation for some to be maintained and spread in diverse bacterial communities. Moreover, phage isolation and host range determination rarely consider the phage ecological context, likely biasing our notion on phage specificity. Here we isolated and characterized a novel group of six promiscuous phages, named Atoyac, existing in rivers and sewage by using a diverse collection of over 600 bacteria retrieved from the same environments as potential hosts. These podophages isolated from different regions in Mexico display a remarkably broad host range, infecting bacteria from six genera: , , , , , and Atoyac phage genomes are ∼42 kb long and highly similar to each other, but not to those currently available in genome and metagenome public databases. Detailed comparison of the phages' efficiency of plating (EOP) revealed variation among bacterial genera, implying a cost associated with infection of distant hosts, and between phages, despite their sequence similarity. We show, through experimental evolution in single or alternate hosts of different genera, that efficiency of plaque production is highly dynamic and tends toward optimization in hosts rendering low plaque formation. However, adaptation to distinct hosts differed between similar phages; whereas one phage optimized its EOP in all tested hosts, the other reduced plaque production in one host, suggesting that propagation in multiple bacteria may be key to maintain promiscuity in some viruses. Our study expands our knowledge of the virosphere and uncovers bacterium-phage interactions overlooked in natural systems. In natural environments, phages coexist and interact with a broad variety of bacteria, posing a conundrum for narrow-host-range phage maintenance in diverse communities. This context is rarely considered in the study of host-phage interactions, typically focused on narrow-host-range viruses and their infectivity in target bacteria isolated from sources distinct to where the phages were retrieved from. By studying phage-host interactions in bacteria and viruses isolated from river microbial communities, we show that novel phages with promiscuous host range encompassing multiple bacterial genera can be found in the environment. Assessment of hundreds of interactions in diverse hosts revealed that similar phages exhibit different infection efficiency and adaptation patterns. Understanding host range is fundamental in our knowledge of bacterium-phage interactions and their impact on microbial communities. The dynamic nature of phage promiscuity revealed in our study has implications in different aspects of phage research such as horizontal gene transfer or phage therapy.
噬菌体通常被描述为具有物种特异性甚至菌株特异性，这意味着对于一些噬菌体来说，在不同的细菌群落中维持和传播存在内在限制。此外，噬菌体的分离和宿主范围的确定很少考虑噬菌体的生态背景，这可能会使我们对噬菌体特异性的认识产生偏差。在这里，我们通过使用从与潜在宿主相同环境中获取的600多种不同细菌，分离并鉴定了一组新的六种泛嗜性噬菌体，命名为阿托亚克噬菌体，它们存在于河流和污水中。这些从墨西哥不同地区分离出的肌尾噬菌体显示出非常广泛的宿主范围，可感染六个属的细菌： 、 、 、 、 和 。阿托亚克噬菌体基因组长度约为42 kb，彼此高度相似，但与基因组和宏基因组公共数据库中目前可用的噬菌体基因组不同。对噬菌体的平板接种效率（EOP）进行详细比较后发现，不同细菌属之间存在差异，这意味着感染远距离宿主存在成本，而且尽管噬菌体序列相似，但不同噬菌体之间也存在差异。我们通过在不同属的单一或交替宿主中进行实验进化表明，噬菌斑产生效率具有高度动态性，并且在形成噬菌斑较少的宿主中倾向于优化。然而，相似噬菌体对不同宿主的适应性不同；一种噬菌体在所有测试宿主中优化了其EOP，而另一种噬菌体在一种宿主中降低了噬菌斑产生，这表明在多种细菌中繁殖可能是一些病毒维持泛嗜性的关键。我们的研究扩展了我们对病毒圈的认识，并揭示了自然系统中被忽视的细菌 - 噬菌体相互作用。在自然环境中，噬菌体与各种各样的细菌共存并相互作用，这给在不同群落中维持宿主范围狭窄的噬菌体带来了难题。在宿主 - 噬菌体相互作用的研究中，这种情况很少被考虑，该研究通常集中在宿主范围狭窄的病毒及其对从与噬菌体来源不同的地方分离出的目标细菌的感染性上。通过研究从河流微生物群落中分离出的细菌和病毒之间的噬菌体 - 宿主相互作用，我们表明在环境中可以发现具有包括多个细菌属的泛嗜性宿主范围的新型噬菌体。对不同宿主中数百种相互作用的评估表明，相似的噬菌体表现出不同的感染效率和适应模式。了解宿主范围是我们认识细菌 - 噬菌体相互作用及其对微生物群落影响的基础。我们研究中揭示的噬菌体泛嗜性的动态性质在噬菌体研究的不同方面具有影响，如水平基因转移或噬菌体治疗。
