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The mechanism of bacterial defense system DdmDE from Lactobacillus casei

Cell Research volume 34, pages 873–876 (2024)Cite this article

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Dear Editor,

Prokaryotes have evolved a multitude of defense systems that confer immunity against invasive mobile genetic elements.1,2,3,4,5 A two-gene DNA defense module DdmDE system is found in Vibrionaceae and Lactobacillaceae family and imposes fitness advantages to the bacteria by eliminating invasive plasmids.6 DdmD encodes a fusion protein comprising an N-terminal superfamily 2 helicase and a C-terminal PD-(D/E)XK superfamily nuclease, while DdmE is a putative prokaryotic Argonaute-like protein that frequently engages in bacterial immunity. Although recent studies described the function and structure of DdmDE from Vibrio cholerae,6,7,8,9 the mechanistic basis by which the DdmDE system detects and degrades plasmids is not fully understood. In particular, the process by which DdmD dimer dissociates and how the DNA is captured by the nuclease domain for degradation remain elusive.

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Fig. 1: Functional analysis and cryo-EM structures of DdmDE system from Lactobacillus casei.

Data availability

The atomic coordinates of LcDdmD-fork DNA, LcDdmE-gDNA-bubbleDNA, and LcDdmDE-guide-bubbleDNA have been deposited in the RCSB PDB under accession numbers 9IX4, 9IW3 and 9IXM, respectively, and the corresponding cryo-EM maps have also been deposited in the EMDB under accession numbers EMD-60964, EMD-60944, and EMD-60973, respectively.

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Acknowledgements

We thank the Instrument Analysis Center (IAC) at Shanghai Jiao Tong University for cryo-EM data collection. This work is supported by the National Key R&D Program of China (2023YFC3402300), STI2030-Major Projects (2021ZD0203400), the National Natural Science Foundation of China (32271330; 82321005; 82304614).

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Author notes

  1. These authors contributed equally: Pingping Huang, Purui Yan, Lijie Guo.

Authors and Affiliations

  1. Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China

    Pingping Huang, Purui Yan, Lijie Guo, Wenying Fei, Zhaoxing Li, Jingxian Liu, Jianping Kong, Yue Yao, Yibei Xiao & Meirong Chen

  2. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China

    Pingping Huang, Purui Yan, Lijie Guo, Wenying Fei, Zhaoxing Li, Jingxian Liu, Jianping Kong, Yue Yao, Meiling Lu, Yibei Xiao & Meirong Chen

  3. Chongqing Innovation Institute of China Pharmaceutical University, Chongqing, China

    Meiling Lu, Yibei Xiao & Meirong Chen

  4. Department of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu, China

    Meiling Lu

  5. Engineering Research Center for Anti-infective Drug Discovery, Ministry of Education (ERCADD), Nanjing, Jiangsu, China

    Yibei Xiao

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Contributions

M.C. and Y.X. directed the research. P.H., P.Y., L.G., W.F., J.L., J.K. and Y.Y. performed experiments. M.C., P.H. and Z.L. determined cryo-EM structures. M.C., Y.X., P.H., P.Y., L.G. and M.L. analyzed data. M.C. and Y.X. wrote the manuscript.

Corresponding authors

Correspondence to Yibei Xiao or Meirong Chen.

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The authors declare no competing interests.

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Huang, P., Yan, P., Guo, L. et al. The mechanism of bacterial defense system DdmDE from Lactobacillus casei. Cell Res 34, 873–876 (2024). https://doi.org/10.1038/s41422-024-01042-y

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