Discovery of multiple anti-CRISPRs highlights anti-defense gene clustering in mobile genetic elements.

Discovery of multiple anti-CRISPRs highlights anti-defense gene clustering in mobile genetic elements.
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DOI:
10.1038/s41467-020-19415-3
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发表时间:
2020-11-06
影响因子:
16.6
通讯作者:
Bondy-Denomy J
Bondy-Denomy J
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Pinilla-Redondo R;Shehreen S;Marino ND;Fagerlund RD;Brown CM;Sørensen SJ;Fineran PC;Bondy-Denomy J

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许多原核生物使用CRISPR-CAS系统来对抗入侵的移动遗传元件(MGES)。作为回应,一些MGES已经开发出包括抗CRISPR(ACR)蛋白在内的绕过免疫的策略;然而,这种免疫逃避策略的多样性、分布和活性谱在很大程度上仍不清楚。在这里,我们报告了通过分析与保守的ACR相关(ACA)基因aca5相邻的候选基因来发现新的ACR,这些候选基因与I-F(假单胞菌、细小杆菌和沙雷氏菌)、I-E(假单胞菌和沙雷氏菌)和I-C(假单胞菌)的I型系统相比较。我们在肠杆菌科和假单胞菌中发现了11个编码在染色体和染色体外MGES上的I-F和/或I-E类抗CRISPR基因,以及另外一个ACA(ACA9)。ACR基因不仅与其他ACR基因相关,还与编码不同细菌防御系统抑制物的基因相关。因此,我们的发现强调了利用ACR基因座邻域来识别以前未描述的反防御系统的可能性。可移动的遗传元件已经进化出抗CRISPR(ACR)蛋白来绕过原核生物CRISPR-Cas系统提供的免疫。在这里,作者鉴定了11个编码在移动遗传元件上的I型ACR,并表明ACR基因座邻域可以用来发现其他细菌防御系统的抑制剂。
Many prokaryotes employ CRISPR–Cas systems to combat invading mobile genetic elements (MGEs). In response, some MGEs have developed strategies to bypass immunity, including anti-CRISPR (Acr) proteins; yet the diversity, distribution and spectrum of activity of this immune evasion strategy remain largely unknown. Here, we report the discovery of new Acrs by assaying candidate genes adjacent to a conserved Acr-associated (Aca) gene, aca5, against a panel of six type I systems: I–F (Pseudomonas, Pectobacterium, and Serratia), I–E (Pseudomonas and Serratia), and I–C (Pseudomonas). We uncover 11 type I–F and/or I–E anti-CRISPR genes encoded on chromosomal and extrachromosomal MGEs within Enterobacteriaceae and Pseudomonas, and an additional Aca (aca9). The acr genes not only associate with other acr genes, but also with genes encoding inhibitors of distinct bacterial defense systems. Thus, our findings highlight the potential exploitation of acr loci neighborhoods for the identification of previously undescribed anti-defense systems. Mobile genetic elements have evolved anti-CRISPR (Acr) proteins to bypass the immunity provided by prokaryotic CRISPR–Cas systems. Here, the authors identify 11 type I Acrs encoded on mobile genetic elements, and show that acr loci neighborhoods can be used to discover inhibitors of other bacterial defense systems.
DOI: 10.1126/science.aba0372
发表时间: 2020-08-28
期刊: Science (New York, N.Y.)
影响因子: --
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