一种新的抗 CRISPR 基因促进了肺炎克雷伯氏菌中耐药质粒的传播。

A new anti-CRISPR gene promotes the spread of drug-resistance plasmids in Klebsiella pneumoniae.

机构信息

Department of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Key Laboratory of Synthetic Biology, State Key Laboratory of Plant Design, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200032, China.

出版信息

Nucleic Acids Res. 2024 Aug 12;52(14):8370-8384. doi: 10.1093/nar/gkae516.

DOI:10.1093/nar/gkae516

PMID:38888121

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11317147/

Abstract

The Klebsiella pneumoniae (K. pneumoniae, Kp) populations carrying both resistance-encoding and virulence-encoding mobile genetic elements (MGEs) significantly threaten global health. In this study, we identified a new anti-CRISPR gene (acrIE10) on a conjugative plasmid with self-target sequence in K. pneumoniae with type I-E* CRISPR-Cas system. AcrIE10 interacts with the Cas7* subunit of K. pneumoniae I-E* CRISPR-Cas system. The crystal structure of the AcrIE10-KpCas7* complex suggests that AcrIE10 suppresses the I-E* CRISPR-Cas by binding directly to Cas7 to prevent its hexamerization, thereby preventing the surveillance complex assembly and crRNA loading. Bioinformatic and functional analyses revealed that AcrIE10 is functionally widespread across diverse species. Our study reports a novel anti-CRISPR and highlights its potential role in spreading resistance and virulence among pathogens.

摘要

携带耐药性编码和毒力编码移动遗传元件（MGE）的肺炎克雷伯菌（K. pneumoniae，Kp）种群对全球健康构成重大威胁。在本研究中，我们在具有 I 型-ECRISPR-Cas 系统的肺炎克雷伯菌中发现了一种新型抗 CRISPR 基因（acrIE10），它位于一个具有自我靶向序列的可接合质粒上。AcrIE10 与肺炎克雷伯菌 I-ECRISPR-Cas 系统的 Cas7亚基相互作用。AcrIE10-KpCas7复合物的晶体结构表明，AcrIE10 通过直接结合 Cas7 来抑制 I-E*CRISPR-Cas，从而阻止其六聚体形成，防止监视复合物组装和 crRNA 加载。生物信息学和功能分析表明，AcrIE10 在不同物种中具有广泛的功能。我们的研究报告了一种新型的抗 CRISPR，并强调了它在传播病原体中的耐药性和毒力方面的潜在作用。