Elliott Josie F K, Cozens Keira, Cai Yueyi, Waugh Gretel, Watson Bridget N, Westra Edze, Taylor Tiffany B
Milner Centre for Evolution, Department of Life Sciences, University of Bath, Bath BA2 7AY, UK.
ESI, University of Exeter - Cornwall Campus, Penryn TR10 9FE, Cornwall, UK.
Philos Trans R Soc Lond B Biol Sci. 2025 Sep 4;380(1934):20240473. doi: 10.1098/rstb.2024.0473.
CRISPR-Cas systems can provide adaptive, heritable immunity to their prokaryotic hosts against invading genetic material such as phages. It is clear that the importance of acquiring CRISPR-Cas immunity to anti-phage defence varies across environments, but it is less clear if and how this varies across different phages. To explore this, we created a synthetic, modular version of the type I-F CRISPR-Cas system of . We used this synthetic system to test CRISPR-Cas interference against a panel of 13 diverse phages using engineered phage-targeting spacers. We observed complete protection against eight of these phages, both lytic and lysogenic and with a range of infectivity profiles. However, for two phages, CRISPR-Cas interference was only partially protective in high-nutrient conditions, yet completely protective in low-nutrient conditions. This work demonstrates that nutrient conditions modulate the strength of CRISPR-Cas immunity and highlights the importance of environmental conditions when screening defence systems for their efficacy against various phages.This article is part of the discussion meeting issue 'The ecology and evolution of bacterial immune systems'.
CRISPR-Cas系统可为其原核宿主提供适应性、可遗传的免疫，以抵御诸如噬菌体等入侵的遗传物质。很明显，获得CRISPR-Cas免疫对噬菌体防御的重要性在不同环境中有所不同，但对于这种差异是否以及如何在不同噬菌体之间存在，目前尚不清楚。为了探究这一点，我们构建了一种合成的、模块化的I-F型CRISPR-Cas系统。我们使用这个合成系统，通过工程化的靶向噬菌体间隔序列，测试了CRISPR-Cas对一组13种不同噬菌体的干扰作用。我们观察到，对于其中8种噬菌体，无论是裂解性还是溶原性的，以及具有一系列感染性特征的噬菌体，均能提供完全保护。然而，对于两种噬菌体，CRISPR-Cas干扰在高营养条件下仅具有部分保护作用，而在低营养条件下则具有完全保护作用。这项工作表明营养条件可调节CRISPR-Cas免疫的强度，并突出了在筛选防御系统针对各种噬菌体的功效时环境条件的重要性。本文是“细菌免疫系统的生态学与进化”讨论会议题的一部分。
