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PreprintCited by 58Bacterial biofilms and quorum sensingBacterial Genetics and BiotechnologyEscherichia coli research studies

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Autoinducer-2 and bile salts induce c-di-GMP synthesis to repress the T3SS via the CesD/SycD/LcrH family of chaperones

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Li, Shuyu, Sun, Hengxi, Li, Jianghan, Zhao, Yujiao, Wang, Ruiying, Xu, Lei, Duan, Chongyi, Li, Jialin, Wang, Zhuo, Liu, Qinmeng, Wang, Yao, Ouyang, Songying, Shen, Xihui, Zhang, Lei·2022·Nature Communications
DOI 10.21203/rs.3.rs-1101635/v1PMC PMC9637222

Preprint — published as 10.1038/s41467-022-34607-9 · Paper page

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Abstract

Cyclic di-GMP (c-di-GMP) is a bacterial second messenger that transduces extracellular stimuli into intracellular responses, efficiently coordinating a plethora of important biological processes. Low levels of c-di-GMP are often associated with highly virulent behavior that depends on the type III secretion system (T3SS) effectors encoded, whereas elevated levels of c-di-GMP lead to the repression of T3SSs. However, extracellular signals that modulate c-di-GMP metabolism to control T3SSs and the underlying mechanisms remain largely obscure. Here, we identify a GAPES1 domain-containing diguanylate cyclase (DGC) YeaJ that senses the quorum sensing signal autoinducer-2 (AI-2) to repress T3SS-1 gene expression in Salmonella enterica serovar Typhimurium. YeaJ homologs capable of sensing AI-2 are present in many other species belonging to Enterobacterales. We also reveal that bile components taurocholate and taurodeoxycholate bind to the periplasmic sensory domain of the DGC YedQ to induce intracellular accumulation of c-di-GMP, thus repressing the expression of T3SS-1 genes. Further, we found that c-di-GMP negatively controls the function of T3SSs through binding to the widely conserved CesD/SycD/LcrH family of T3SS chaperones. Our results support a model in which bacteria sense changes in population density and host-derived cues to regulate c-di-GMP synthesis, thereby modulating the activity of T3SSs via a c-di-GMP-responsive T3SS chaperone.

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Metadata

Authors
Li, S., Sun, H., Li, J., Zhao, Y., Wang, R., Xu, L., Duan, C., Li, J., Wang, Z., Liu, Q., Wang, Y., Ouyang, S., Shen, X., & Zhang, L.
Affiliations
  • Northwest A&F University (CN)
  • Fujian Normal University (CN)
Corresponding author
  • Ouyang, Songying
  • Shen, Xihui
  • Zhang, Lei
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2022-09-22
Volume
13
Issue
1
Pages
6684-6684
ISSN
2041-1723 (ISSN-L)
DOI
10.21203/rs.3.rs-1101635/v1
PMC
PMC9637222
OpenAlex
W4308451496
Cited by
58
References
1
Citations by year
2026: 17 · 2025: 30 · 2024: 6 · 2023: 5
FWCI
3.35
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Nanyang Technological University
  • National Natural Science Foundation of China (31,725,003, 32170048, 82172287, 82225028, 2018YFA0901200)
  • Chinese Academy of Sciences
  • Northwest A and F University
  • Institute of Microbiology, Chinese Academy of Sciences
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
Keywords
c-di-GMP, autoinducer-2, quorum sensing, type III secretion system, diguanylate cyclase, bile salts, taurocholate, taurodeoxycholic acid, Salmonella typhimurium, Enterobacterales, bacterial virulence regulation
MeSH terms
Bacterial Proteins, Bile Acids and Salts, Cyclic GMP, Salmonella typhimurium, Gene Expression Regulation, Bacterial, Biofilms, Molecular Chaperones, Escherichia coli Proteins

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