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

• Published in: Nature communications 2023-11, Vol.14 (1), p.7502-7502, Article 7502
• Main Authors: Li, Shuyu, Liu, Qinmeng, Duan, Chongyi, Li, Jialin, Sun, Hengxi, Xu, Lei, Yang, Qiao, Wang, Yao, Shen, Xihui, Zhang, Lei
• Format: Article
• Language: English
• Subjects: 38; 38/77; 38/91; 631/208/200; 631/326/325/1506; 631/326/41/1969; 631/326/421; 631/337/572; 82/1; 82/51; 82/58; 82/83; Bacteria; Binding; Biological activity; Deoxyribonucleic acid; DNA; Gene expression; Gene silencing; Genes; Gram-negative bacteria; H-NS protein; Humanities and Social Sciences; multidisciplinary; Proteins; Salmonella; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-43442-5

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. H-NS is a global regulatory protein that represses expression of many genes in bacteria. Here, Li et al. show that a second messenger, cyclic di-GMP, binds to H-NS and inhibits its binding to DNA, thus relieving H-NS-mediated transcriptional silencing.