c-di-GMP inhibits the DNA binding activity of H-NS in Salmonella

Shuyu Li, Qinmeng Liu, Chongyi Duan, Jialin Li, Hengxi Sun, Lei Xu, Qiao Yang, Yao Wang, Xihui Shen () and Lei Zhang ()
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Shuyu Li: Northwest A&F University
Qinmeng Liu: Northwest A&F University
Chongyi Duan: Northwest A&F University
Jialin Li: Northwest A&F University
Hengxi Sun: Northwest A&F University
Lei Xu: Northwest A&F University
Qiao Yang: Zhejiang Ocean University
Yao Wang: Northwest A&F University
Xihui Shen: Northwest A&F University
Lei Zhang: Northwest A&F University

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: Abstract Cyclic di-GMP (c-di-GMP) is a second messenger that transduces extracellular stimuli into cellular responses and regulates various biological processes in bacteria. H-NS is a global regulatory protein that represses expression of many genes, but how H-NS activity is modulated by environmental signals remains largely unclear. Here, we show that high intracellular c-di-GMP levels, induced by environmental cues, relieve H-NS-mediated transcriptional silencing in Salmonella enterica serovar Typhimurium. We find that c-di-GMP binds to the H-NS protein to inhibit its binding to DNA, thus derepressing genes silenced by H-NS. However, c-di-GMP is unable to displace H-NS from DNA. In addition, a K107A mutation in H-NS abolishes response to c-di-GMP but leaves its DNA binding activity unaffected in vivo. Our results thus suggest a mechanism by which H-NS acts as an environment-sensing regulator in Gram-negative bacteria.

Date: 2023
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DOI: 10.1038/s41467-023-43442-5

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