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

  • Xiaocui Ling,
  • Xiao Liu,
  • Kun Wang,
  • Minhao Guo,
  • Yanzhe Ou,
  • Danting Li,
  • Yulin Xiang,
  • Jiachen Zheng,
  • Lihua Hu,
  • Hongyun Zhang,
  • Weihui Li

摘要

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.