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 and Weihui Li ()
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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

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-44774-6

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