CRISPR-Cas system: diversity and regulation in Enterobacteriaceae supplementarydata

Insights into the arms race between bacteria and invading mobile genetic elements have revealed the intricacies of the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system and the counter-defenses of bacteriophages. Incredible spacer diversity but significant spacer conservation among species/subspecies dictates the specificity of the CRISPR-Cas system. Researchers have exploited this feature to type/subtype the bacterial strains, devise targeted antimicrobials and regulate gene expression. This review focuses on the nuances of the CRISPR-Cas systems in Enterobacteriaceae that predominantly harbor type I-E and I-F CRISPR systems. We discuss the systems’ regulation by the global regulators, H-NS, LeuO, LRP, cAMP receptor protein and other regulators in response to environmental stress. We further discuss the regulation of noncanonical functions like DNA repair pathways, biofilm formation, quorum sensing and virulence by the CRISPR-Cas system. The review comprehends multiple facets of the CRISPR-Cas system in Enterobacteriaceae including its diverse attributes, association with genetic features, regulation and gene regulatory mechanisms.对细菌与入侵移动遗传元件之间军备竞赛的研究，揭示了成簇规律间隔短回文重复序列（CRISPR）-Cas系统的复杂运作机制，以及噬菌体的反击防御策略。不同物种/亚种间的间隔序列（spacer）虽具有极高的多样性，但同时存在显著的保守性，这一特征决定了CRISPR-Cas系统的特异性。研究人员已利用该特性对细菌菌株进行分型与亚型分型，开发靶向抗菌药物，并实现基因表达的精准调控。本综述聚焦于肠杆菌科（Enterobacteriaceae）中CRISPR-Cas系统的细微特征，该科细菌主要携带I-E型与I-F型CRISPR系统。我们探讨了全局调控因子H-NS、LeuO、LRP、环腺苷酸受体蛋白（cAMP receptor protein）及其他调控因子，在应对环境胁迫时对该系统的调控作用。此外，我们还论述了CRISPR-Cas系统对多项非经典功能的调控，包括DNA修复通路、生物被膜形成、群体感应（quorum sensing）以及毒力调控。本综述涵盖了肠杆菌科中CRISPR-Cas系统的多个研究维度，包括其多样的生物学特性、与遗传特征的关联、调控模式及基因调控机制。