Grazia Vizzarro, Alexandre Lemopoulos, David William Adams, Melanie Blokesch
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Here, we demonstrate that the T1RM system is active, methylates the host genomes of a representative set of 7PET strains, and identify a specific recognition sequence that targets non-methylated plasmids for restriction. We go on to show that the two genes embedded within the T1RM system encode a novel two-protein modification-dependent restriction system related to the GmrSD family of type IV restriction enzymes. Indeed, we show that this system has potent anti-phage activity against diverse members of the <i>Tevenvirinae</i>, a subfamily of bacteriophages with hypermodified genomes. Taken together, these results expand our understanding of how this highly conserved genomic island contributes to the defense of pandemic <i>V. cholerae</i> against foreign DNA.</p><p><strong>Importance: </strong>Defense systems are immunity systems that allow bacteria to counter the threat posed by bacteriophages and other mobile genetic elements. Although these systems are numerous and highly diverse, the most common types are restriction enzymes that can specifically recognize and degrade non-self DNA. Here, we show that the <i>Vibrio</i> pathogenicity island 2, present in the pathogen <i>Vibrio cholerae</i>, encodes two types of restriction systems that use distinct mechanisms to sense non-self DNA. The first system is a classical Type I restriction-modification system, and the second is a novel modification-dependent type IV restriction system that recognizes hypermodified cytosines. Interestingly, these systems are embedded within each other, suggesting that they are complementary to each other by targeting both modified and non-modified phages.</p>","PeriodicalId":15107,"journal":{"name":"Journal of Bacteriology","volume":" ","pages":"e0014524"},"PeriodicalIF":2.7000,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411939/pdf/","citationCount":"0","resultStr":"{\"title\":\"<i>Vibrio cholerae</i> pathogenicity island 2 encodes two distinct types of restriction systems.\",\"authors\":\"Grazia Vizzarro, Alexandre Lemopoulos, David William Adams, Melanie Blokesch\",\"doi\":\"10.1128/jb.00145-24\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>In response to predation by bacteriophages and invasion by other mobile genetic elements such as plasmids, bacteria have evolved specialized defense systems that are often clustered together on genomic islands. The O1 El Tor strains of <i>Vibrio cholerae</i> responsible for the ongoing seventh cholera pandemic (7PET) contain a characteristic set of genomic islands involved in host colonization and disease, many of which contain defense systems. Notably, <i>Vibrio</i> pathogenicity island 2 contains several characterized defense systems as well as a putative type I restriction-modification (T1RM) system, which, interestingly, is interrupted by two genes of unknown function. Here, we demonstrate that the T1RM system is active, methylates the host genomes of a representative set of 7PET strains, and identify a specific recognition sequence that targets non-methylated plasmids for restriction. We go on to show that the two genes embedded within the T1RM system encode a novel two-protein modification-dependent restriction system related to the GmrSD family of type IV restriction enzymes. Indeed, we show that this system has potent anti-phage activity against diverse members of the <i>Tevenvirinae</i>, a subfamily of bacteriophages with hypermodified genomes. Taken together, these results expand our understanding of how this highly conserved genomic island contributes to the defense of pandemic <i>V. cholerae</i> against foreign DNA.</p><p><strong>Importance: </strong>Defense systems are immunity systems that allow bacteria to counter the threat posed by bacteriophages and other mobile genetic elements. Although these systems are numerous and highly diverse, the most common types are restriction enzymes that can specifically recognize and degrade non-self DNA. Here, we show that the <i>Vibrio</i> pathogenicity island 2, present in the pathogen <i>Vibrio cholerae</i>, encodes two types of restriction systems that use distinct mechanisms to sense non-self DNA. The first system is a classical Type I restriction-modification system, and the second is a novel modification-dependent type IV restriction system that recognizes hypermodified cytosines. 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引用次数: 0
摘要
为了应对噬菌体的捕食和质粒等其他移动遗传因子的入侵,细菌进化出了专门的防御系统,这些系统通常聚集在基因组岛上。造成目前第七次霍乱大流行(7PET)的霍乱弧菌 O1 El Tor 菌株含有一组参与宿主定殖和疾病的特征性基因组岛,其中许多含有防御系统。值得注意的是,致病性弧菌岛 2 包含多个特征性防御系统以及一个假定的 I 型限制性修饰(T1RM)系统,有趣的是,该系统被两个功能未知的基因打断。在这里,我们证明了 T1RM 系统是活跃的,它能使一组具有代表性的 7PET 菌株的宿主基因组甲基化,并确定了一个特定的识别序列,该序列能对非甲基化质粒进行限制。我们进而证明,T1RM 系统中的两个基因编码一种新型的双蛋白修饰依赖性限制系统,与 GmrSD 家族的 IV 型限制酶有关。事实上,我们发现该系统对特文病毒科(Tevenvirinae)的不同成员具有很强的抗噬菌体活性,特文病毒科是一个具有超修饰基因组的噬菌体亚家族。总之,这些结果拓展了我们对这一高度保守的基因组岛如何帮助大流行性霍乱弧菌抵御外来 DNA 的理解:防御系统是一种免疫系统,可使细菌抵御噬菌体和其他移动遗传因子的威胁。虽然这些系统种类繁多且高度多样化,但最常见的类型是限制酶,它能特异性地识别和降解非自身 DNA。在这里,我们发现病原体霍乱弧菌中的致病性弧菌岛 2 编码两种类型的限制性系统,它们使用不同的机制来感知非自身 DNA。第一种系统是经典的 I 型限制-修饰系统,第二种是新型的依赖修饰的 IV 型限制系统,它能识别超修饰的胞嘧啶。有趣的是,这些系统彼此内嵌,表明它们通过靶向修饰和非修饰噬菌体而相互补充。
Vibrio cholerae pathogenicity island 2 encodes two distinct types of restriction systems.
In response to predation by bacteriophages and invasion by other mobile genetic elements such as plasmids, bacteria have evolved specialized defense systems that are often clustered together on genomic islands. The O1 El Tor strains of Vibrio cholerae responsible for the ongoing seventh cholera pandemic (7PET) contain a characteristic set of genomic islands involved in host colonization and disease, many of which contain defense systems. Notably, Vibrio pathogenicity island 2 contains several characterized defense systems as well as a putative type I restriction-modification (T1RM) system, which, interestingly, is interrupted by two genes of unknown function. Here, we demonstrate that the T1RM system is active, methylates the host genomes of a representative set of 7PET strains, and identify a specific recognition sequence that targets non-methylated plasmids for restriction. We go on to show that the two genes embedded within the T1RM system encode a novel two-protein modification-dependent restriction system related to the GmrSD family of type IV restriction enzymes. Indeed, we show that this system has potent anti-phage activity against diverse members of the Tevenvirinae, a subfamily of bacteriophages with hypermodified genomes. Taken together, these results expand our understanding of how this highly conserved genomic island contributes to the defense of pandemic V. cholerae against foreign DNA.
Importance: Defense systems are immunity systems that allow bacteria to counter the threat posed by bacteriophages and other mobile genetic elements. Although these systems are numerous and highly diverse, the most common types are restriction enzymes that can specifically recognize and degrade non-self DNA. Here, we show that the Vibrio pathogenicity island 2, present in the pathogen Vibrio cholerae, encodes two types of restriction systems that use distinct mechanisms to sense non-self DNA. The first system is a classical Type I restriction-modification system, and the second is a novel modification-dependent type IV restriction system that recognizes hypermodified cytosines. Interestingly, these systems are embedded within each other, suggesting that they are complementary to each other by targeting both modified and non-modified phages.
期刊介绍:
The Journal of Bacteriology (JB) publishes research articles that probe fundamental processes in bacteria, archaea and their viruses, and the molecular mechanisms by which they interact with each other and with their hosts and their environments.