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

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 environment...

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Main Authors: Shuyu Li, Qinmeng Liu, Chongyi Duan, Jialin Li, Hengxi Sun, Lei Xu, Qiao Yang, Yao Wang, Xihui Shen, Lei Zhang
Format: Article
Language:English
Published: Nature Portfolio 2023-11-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-43442-5
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author Shuyu Li
Qinmeng Liu
Chongyi Duan
Jialin Li
Hengxi Sun
Lei Xu
Qiao Yang
Yao Wang
Xihui Shen
Lei Zhang
author_facet Shuyu Li
Qinmeng Liu
Chongyi Duan
Jialin Li
Hengxi Sun
Lei Xu
Qiao Yang
Yao Wang
Xihui Shen
Lei Zhang
author_sort Shuyu Li
collection DOAJ
description 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.
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spelling doaj.art-59f746a573ce418fa3507ee53494a5c02023-11-20T09:51:20ZengNature PortfolioNature Communications2041-17232023-11-0114111110.1038/s41467-023-43442-5c-di-GMP inhibits the DNA binding activity of H-NS in SalmonellaShuyu Li0Qinmeng Liu1Chongyi Duan2Jialin Li3Hengxi Sun4Lei Xu5Qiao Yang6Yao Wang7Xihui Shen8Lei Zhang9State Key Laboratory of Crop Stress Biology for Arid Areas, Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F UniversityState Key Laboratory of Crop Stress Biology for Arid Areas, Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F UniversityState Key Laboratory of Crop Stress Biology for Arid Areas, Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F UniversityState Key Laboratory of Crop Stress Biology for Arid Areas, Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F UniversityState Key Laboratory of Crop Stress Biology for Arid Areas, Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F UniversityState Key Laboratory of Crop Stress Biology for Arid Areas, Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F UniversityABI Group, College of Marine Science and Technology, Zhejiang Ocean UniversityState Key Laboratory of Crop Stress Biology for Arid Areas, Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F UniversityState Key Laboratory of Crop Stress Biology for Arid Areas, Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F UniversityState Key Laboratory of Crop Stress Biology for Arid Areas, Shaanxi Key Laboratory of Agricultural and Environmental Microbiology, College of Life Sciences, Northwest A&F UniversityAbstract 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.https://doi.org/10.1038/s41467-023-43442-5
spellingShingle Shuyu Li
Qinmeng Liu
Chongyi Duan
Jialin Li
Hengxi Sun
Lei Xu
Qiao Yang
Yao Wang
Xihui Shen
Lei Zhang
c-di-GMP inhibits the DNA binding activity of H-NS in Salmonella
Nature Communications
title c-di-GMP inhibits the DNA binding activity of H-NS in Salmonella
title_full c-di-GMP inhibits the DNA binding activity of H-NS in Salmonella
title_fullStr c-di-GMP inhibits the DNA binding activity of H-NS in Salmonella
title_full_unstemmed c-di-GMP inhibits the DNA binding activity of H-NS in Salmonella
title_short c-di-GMP inhibits the DNA binding activity of H-NS in Salmonella
title_sort c di gmp inhibits the dna binding activity of h ns in salmonella
url https://doi.org/10.1038/s41467-023-43442-5
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