A DNA phosphorothioation-based Dnd defense system provides resistance against various phages and is compatible with the Ssp defense system
ABSTRACT DndABCDE-catalyzed DNA phosphorothioation (PT), in which the nonbridging oxygen is swapped with a sulfur atom, was first identified in the bacterial genome. Usually, this modification gene cluster is paired with a restriction module consisting of DndF, DndG, and DndH. Although the mechanism...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-08-01
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| Series: | mBio |
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| Online Access: | https://journals.asm.org/doi/10.1128/mbio.00933-23 |
| _version_ | 1797730289641848832 |
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| author | Susu Jiang Ke Chen Yingying Wang Yueying Zhang Yaru Tang Wanqiu Huang Xiaolin Xiong Shi Chen Chao Chen Lianrong Wang |
| author_facet | Susu Jiang Ke Chen Yingying Wang Yueying Zhang Yaru Tang Wanqiu Huang Xiaolin Xiong Shi Chen Chao Chen Lianrong Wang |
| author_sort | Susu Jiang |
| collection | DOAJ |
| description | ABSTRACT DndABCDE-catalyzed DNA phosphorothioation (PT), in which the nonbridging oxygen is swapped with a sulfur atom, was first identified in the bacterial genome. Usually, this modification gene cluster is paired with a restriction module consisting of DndF, DndG, and DndH. Although the mechanisms for the antiphage activity conferred by this Dnd-related restriction and modification (R-M) system have been well characterized, several features remain unclear, including the antiphage spectrum and potential interference with DNA methylation. Recently, a novel PT-related R-M system, composed of the modification module SspABCD paired with a single restriction enzyme, SspE, was revealed to be widespread in the bacterial kingdom, which aroused our interest in the interaction between Dnd- and Ssp-based R-M systems. In this study, we discussed the action of Dnd-related R-M systems against phages and demonstrated that the host could benefit from the protection provided by Dnd-related R-M systems against infection by various lytic phages as well as temperate phages. However, this defense barrier would fail against lysogenic phages. Interestingly, DNA methylation, even in the consensus sequence recognized by the Dnd system, could not weaken the restriction efficiency. Finally, we explored the interaction between Dnd- and Ssp-based R-M systems and found that these two systems were compatible. This study not only expands our knowledge of Dnd-associated R-M systems but also reveals a complex interaction between different defense barriers that coexist in the cell. IMPORTANCE Recently, we decoded the mechanism of Dnd-related R-M systems against genetic parasites. In the presence of exogenous DNA that lacks PT, the macromolecular machine consisting of DndF, DndG, and DndH undergoes conformational changes to perform DNA binding, translocation, and DNA nicking activities and scavenge the foreign DNA. However, several questions remain unanswered, including questions regarding the antiphage spectrum, potential interference by DNA methylation, and interplay with other PT-dependent R-M systems. Here, we revealed that the host could benefit from Dnd-related R-M systems for a broad range of antiphage activities, regardless of the presence of DNA methylation. Furthermore, we demonstrated that the convergence of Dnd- and Ssp-related R-M systems could confer to the host a stronger antiphage ability through the additive suppression of phage replication. This study not only deepens our understanding of PT-related defense barriers but also expands our knowledge of the arms race between bacteria and their predators. |
| first_indexed | 2024-03-12T11:42:07Z |
| format | Article |
| id | doaj.art-e9da0fdf5cb54d5294d80b3d42b26a05 |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-12T11:42:07Z |
| publishDate | 2023-08-01 |
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| series | mBio |
| spelling | doaj.art-e9da0fdf5cb54d5294d80b3d42b26a052023-08-31T15:04:20ZengAmerican Society for MicrobiologymBio2150-75112023-08-0114410.1128/mbio.00933-23A DNA phosphorothioation-based Dnd defense system provides resistance against various phages and is compatible with the Ssp defense systemSusu Jiang0Ke Chen1Yingying Wang2Yueying Zhang3Yaru Tang4Wanqiu Huang5Xiaolin Xiong6Shi Chen7Chao Chen8Lianrong Wang9Department of Gastroenterology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Disease, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University , Wuhan, Hubei, ChinaDepartment of Gastroenterology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Disease, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University , Wuhan, Hubei, ChinaDepartment of Gastroenterology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Disease, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University , Wuhan, Hubei, ChinaDepartment of Gastroenterology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Disease, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University , Wuhan, Hubei, ChinaDepartment of Gastroenterology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Disease, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University , Wuhan, Hubei, ChinaDepartment of Gastroenterology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Disease, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University , Wuhan, Hubei, ChinaDepartment of Gastroenterology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Disease, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University , Wuhan, Hubei, ChinaDepartment of Gastroenterology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Disease, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University , Wuhan, Hubei, ChinaDepartment of Burn and Plastic Surgery, Shenzhen Institute of Translational Medicine, Health Science Center, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University , Shenzhen, Guangdong, ChinaDepartment of Gastroenterology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Disease, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University , Wuhan, Hubei, ChinaABSTRACT DndABCDE-catalyzed DNA phosphorothioation (PT), in which the nonbridging oxygen is swapped with a sulfur atom, was first identified in the bacterial genome. Usually, this modification gene cluster is paired with a restriction module consisting of DndF, DndG, and DndH. Although the mechanisms for the antiphage activity conferred by this Dnd-related restriction and modification (R-M) system have been well characterized, several features remain unclear, including the antiphage spectrum and potential interference with DNA methylation. Recently, a novel PT-related R-M system, composed of the modification module SspABCD paired with a single restriction enzyme, SspE, was revealed to be widespread in the bacterial kingdom, which aroused our interest in the interaction between Dnd- and Ssp-based R-M systems. In this study, we discussed the action of Dnd-related R-M systems against phages and demonstrated that the host could benefit from the protection provided by Dnd-related R-M systems against infection by various lytic phages as well as temperate phages. However, this defense barrier would fail against lysogenic phages. Interestingly, DNA methylation, even in the consensus sequence recognized by the Dnd system, could not weaken the restriction efficiency. Finally, we explored the interaction between Dnd- and Ssp-based R-M systems and found that these two systems were compatible. This study not only expands our knowledge of Dnd-associated R-M systems but also reveals a complex interaction between different defense barriers that coexist in the cell. IMPORTANCE Recently, we decoded the mechanism of Dnd-related R-M systems against genetic parasites. In the presence of exogenous DNA that lacks PT, the macromolecular machine consisting of DndF, DndG, and DndH undergoes conformational changes to perform DNA binding, translocation, and DNA nicking activities and scavenge the foreign DNA. However, several questions remain unanswered, including questions regarding the antiphage spectrum, potential interference by DNA methylation, and interplay with other PT-dependent R-M systems. Here, we revealed that the host could benefit from Dnd-related R-M systems for a broad range of antiphage activities, regardless of the presence of DNA methylation. Furthermore, we demonstrated that the convergence of Dnd- and Ssp-related R-M systems could confer to the host a stronger antiphage ability through the additive suppression of phage replication. This study not only deepens our understanding of PT-related defense barriers but also expands our knowledge of the arms race between bacteria and their predators.https://journals.asm.org/doi/10.1128/mbio.00933-23DNA phosphorothioationDnd systemsSsp systemsrestriction-modification systemsDNA methylationphage resistance |
| spellingShingle | Susu Jiang Ke Chen Yingying Wang Yueying Zhang Yaru Tang Wanqiu Huang Xiaolin Xiong Shi Chen Chao Chen Lianrong Wang A DNA phosphorothioation-based Dnd defense system provides resistance against various phages and is compatible with the Ssp defense system mBio DNA phosphorothioation Dnd systems Ssp systems restriction-modification systems DNA methylation phage resistance |
| title | A DNA phosphorothioation-based Dnd defense system provides resistance against various phages and is compatible with the Ssp defense system |
| title_full | A DNA phosphorothioation-based Dnd defense system provides resistance against various phages and is compatible with the Ssp defense system |
| title_fullStr | A DNA phosphorothioation-based Dnd defense system provides resistance against various phages and is compatible with the Ssp defense system |
| title_full_unstemmed | A DNA phosphorothioation-based Dnd defense system provides resistance against various phages and is compatible with the Ssp defense system |
| title_short | A DNA phosphorothioation-based Dnd defense system provides resistance against various phages and is compatible with the Ssp defense system |
| title_sort | dna phosphorothioation based dnd defense system provides resistance against various phages and is compatible with the ssp defense system |
| topic | DNA phosphorothioation Dnd systems Ssp systems restriction-modification systems DNA methylation phage resistance |
| url | https://journals.asm.org/doi/10.1128/mbio.00933-23 |
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