肺炎克雷伯菌CRISPR-Cas系统及anti-CRISPR蛋白家族研究进展

Research advances in CRISPR-Cas systems and anti-CRISPR protein families in Klebsiella pneumoniae

肺炎克雷伯菌(Klebsiella pneumoniae)在自然界中广泛分布,致病性肺炎克雷伯菌在临床上可以引起广泛感染,如呼吸系统感染、血流感染、肝脓肿及泌尿系统感染等。肺炎克雷伯菌是著名的“质粒收集器”,其基因组可以同时携带多种不同类型的质粒,从而导致临床中不断出现耐药菌株。尤其是近年来高毒力多重耐药菌株亦不断出现,给临床治疗工作带来了极大挑战。因此肺炎克雷伯菌对外源基因特别是耐药以及毒力相关基因的获取能力引起了广大学者的关注。作为细菌的获得性免疫系统,活跃的常间回文重复序列丛集/常间回文重复序列丛集关联蛋白(clustered regularly interspaced palindromic repeats/CRISPR-associated proteins,CRISPR-Cas)系统可以有效阻碍肺炎克雷伯菌基因组中可移动元件的水平转移,特别是接合型质粒的转移。近年来发现一些接合型质粒通过携带anti-CRISPR (Acr)蛋白抑制宿主菌编码的CRISPR-Cas系统活性,逃逸宿主的免疫识别,进而可以有效进行转移。分析数据库中已知肺炎克雷伯菌基因序列结果表明,其基因组中主要的CRISPR-Cas系统类型为I-E型及亚型(I-E*)。研究肺炎克雷伯菌基因组中CRISPR-Cas系统与质粒的分布及转移关系,并研究Acr蛋白在调控CRISPR-Cas系统活性中发挥作用的机制,将为揭示其基因组进化的动力及方向提供线索,为防控高毒力多重耐药菌株提供临床指导。

Klebsiella pneumoniae(Kp) is widely distributed in nature. Pathogenic Kp can cause a wide range of clinical infections,including respiratory infection, bloodstream infection, liver abscess, urinary system infection and so on. As a famous "plasmid collector", Kp can habor different types of plasmids in its genome. As a result, multidrug-resistant(MDR) strains continue to appear in recent years. Especially, the emergence of hypervirulent MDR(hv-MDR) Kp brings great challenges to clinical treatment.Therefore, the ability of Kp to obtain foreign genes, especially drug resistance and virulence-related genes, has attracted the attention of a large number of scholars. As the major acquired immune system in bacteria, the active clustered regularly interspaced palindromic repeats/CRISPR-associated proteins(CRISPR-Cas) system can effectively block the horizontal transfer of mobile elements into the genome of Kp, especially for transfer ability of conjugative plasmids. In recent years, it has been found that some conjugative plasmids carry anti-CRISPR(Acr) protein to inhibit the activity of the CRISPR-Cas system encoded by host bacteria,escape the host immune recognition, and then can effectively transfer between hosts. The sequenced Kp genome showed that the main types of CRISPR-Cas system in its genome were type I-E and subtype I-E*. Therefore, analysis of the relationship between the CRISPR-Cas distribution and transfer ability of plasmid in Kp and further exploration of the mechanism of Acr protein in regulating the activity of CRISPR-Cas, will provide clues and direction to the dynamics of its genome evolution. It will eventually provide clinical guidance for the prevention and control of hv-MDR Kp.