School of Informatics, Computing and Engineering, Indiana University, Bloomington, IN, USA.
BMC Genomics. 2022 Aug 11;23(1):573. doi: 10.1186/s12864-022-08770-8.
CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) systems are adaptive immune systems commonly found in prokaryotes that provide sequence-specific defense against invading mobile genetic elements (MGEs). The memory of these immunological encounters are stored in CRISPR arrays, where spacer sequences record the identity and history of past invaders. Analyzing such CRISPR arrays provide insights into the dynamics of CRISPR-Cas systems and the adaptation of their host bacteria to rapidly changing environments such as the human gut.
In this study, we utilized 601 publicly available Bacteroides fragilis genome isolates from 12 healthy individuals, 6 of which include longitudinal observations, and 222 available B. fragilis reference genomes to update the understanding of B. fragilis CRISPR-Cas dynamics and their differential activities. Analysis of longitudinal genomic data showed that some CRISPR array structures remained relatively stable over time whereas others involved radical spacer acquisition during some periods, and diverse CRISPR arrays (associated with multiple isolates) co-existed in the same individuals with some persisted over time. Furthermore, features of CRISPR adaptation, evolution, and microdynamics were highlighted through an analysis of host-MGE network, such as modules of multiple MGEs and hosts, reflecting complex interactions between B. fragilis and its invaders mediated through the CRISPR-Cas systems.
We made available of all annotated CRISPR-Cas systems and their target MGEs, and their interaction network as a web resource at https://omics.informatics.indiana.edu/CRISPRone/Bfragilis . We anticipate it will become an important resource for studying of B. fragilis, its CRISPR-Cas systems, and its interaction with mobile genetic elements providing insights into evolutionary dynamics that may shape the species virulence and lead to its pathogenicity.
CRISPR-Cas（规律成簇间隔短回文重复序列-CRISPR 相关蛋白）系统是原核生物中常见的适应性免疫系统，为抵抗入侵的移动遗传元件（MGEs）提供序列特异性防御。这些免疫接触的记忆存储在 CRISPR 阵列中，其中间隔序列记录过去入侵者的身份和历史。分析这些 CRISPR 阵列可以深入了解 CRISPR-Cas 系统的动态及其宿主细菌对快速变化的环境（如人类肠道）的适应能力。
在这项研究中，我们利用了 12 名健康个体的 601 个公开可用的脆弱拟杆菌基因组分离物，其中 6 个包括纵向观察，以及 222 个可用的脆弱拟杆菌参考基因组，以更新对脆弱拟杆菌 CRISPR-Cas 动态及其差异活性的理解。对纵向基因组数据的分析表明，一些 CRISPR 阵列结构随时间相对稳定，而另一些结构在某些时期则涉及激进的间隔序列获取，并且在同一个体中存在多种 CRISPR 阵列（与多个分离物相关），其中一些在长时间内持续存在。此外，通过宿主-MGE 网络的分析突出了 CRISPR 适应、进化和微动态的特征，例如多个 MGE 和宿主的模块，反映了脆弱拟杆菌与其入侵物之间通过 CRISPR-Cas 系统介导的复杂相互作用。
我们提供了所有注释的 CRISPR-Cas 系统及其靶标 MGEs 以及它们的相互作用网络，作为一个网络资源在 https://omics.informatics.indiana.edu/CRISPRone/Bfragilis 上可用。我们预计它将成为研究脆弱拟杆菌、其 CRISPR-Cas 系统及其与移动遗传元件相互作用的重要资源，深入了解可能影响物种毒力并导致其致病性的进化动态。
