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Lsr2 acts as a cyclic di-GMP receptor that promotes keto-mycolic acid synthesis and biofilm formation in mycobacteria

Author

Listed:
  • Xiaocui Ling

    (Guangxi University)

  • Xiao Liu

    (Guangxi University)

  • Kun Wang

    (Guangxi University)

  • Minhao Guo

    (Guangxi University)

  • Yanzhe Ou

    (Guangxi University)

  • Danting Li

    (Guangxi University)

  • Yulin Xiang

    (Guangxi University)

  • Jiachen Zheng

    (Guangxi University)

  • Lihua Hu

    (Guangxi University)

  • Hongyun Zhang

    (Guangxi University)

  • Weihui Li

    (Guangxi University)

Abstract

Cyclic di-GMP (c-di-GMP) is a second messenger that promotes biofilm formation in several bacterial species, but the mechanisms are often unclear. Here, we report that c-di-GMP promotes biofilm formation in mycobacteria in a manner dependent on the nucleoid-associated protein Lsr2. We show that c-di-GMP specifically binds to Lsr2 at a ratio of 1:1. Lsr2 upregulates the expression of HadD, a (3R)-hydroxyacyl-ACP dehydratase, thus promoting the synthesis of keto-mycolic acid and biofilm formation. Thus, Lsr2 acts as a c-di-GMP receptor that links the second messenger’s function to lipid synthesis and biofilm formation in mycobacteria.

Suggested Citation

  • Xiaocui Ling & Xiao Liu & Kun Wang & Minhao Guo & Yanzhe Ou & Danting Li & Yulin Xiang & Jiachen Zheng & Lihua Hu & Hongyun Zhang & Weihui Li, 2024. "Lsr2 acts as a cyclic di-GMP receptor that promotes keto-mycolic acid synthesis and biofilm formation in mycobacteria," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44774-6
    DOI: 10.1038/s41467-024-44774-6
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    References listed on IDEAS

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    1. Poushali Chakraborty & Sapna Bajeli & Deepak Kaushal & Bishan Dass Radotra & Ashwani Kumar, 2021. "Biofilm formation in the lung contributes to virulence and drug tolerance of Mycobacterium tuberculosis," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    2. Cong Liu & Di Sun & Jiawen Liu & Ying Chen & Xuge Zhou & Yunrui Ru & Jingrong Zhu & Weijie Liu, 2022. "cAMP and c-di-GMP synergistically support biofilm maintenance through the direct interaction of their effectors," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
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    4. Weihui Li & Tao Cui & Lihua Hu & Ziqing Wang & Zongqiang Li & Zheng-Guo He, 2015. "Cyclic diguanylate monophosphate directly binds to human siderocalin and inhibits its antibacterial activity," Nature Communications, Nature, vol. 6(1), pages 1-9, November.
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