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PreprintCited by 25Bacterial Genetics and BiotechnologyEscherichia coli research studiesVibrio bacteria research studies

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Co-Component Signal Transduction Systems: fast-evolving virulence regulation cassettes discovered in enteric bacteria

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Kinch, Lisa N., Cong, Qian, Jaishankar, Jananee, Orth, Kim·2022·Proceedings of the National Academy of Sciences
DOI 10.1101/2022.04.08.487670PMC PMC9214523

Preprint — published as 10.1073/pnas.2203176119

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Abstract

Bacterial signal transduction systems sense changes in the environment and transmit these signals to control cellular responses. The simplest one-component signal transduction systems include an input sensor domain and an output response domain encoded in a single protein chain. Alternately, two-component signal transduction systems transmit signals by phosphorelay between input and output domains from separate proteins. The membrane tethered periplasmic bile acid sensor that activates the Vibrio parahaemolyticus type III secretion system adopts an obligate heterodimer of two proteins encoded by partially overlapping VtrA and VtrC genes. This co-component signal transduction system binds bile acid using a lipocalin-like domain in VtrC and transmits the signal through the membrane to a cytoplasmic DNA-binding transcription factor in VtrA. Using the domain and operon organization of VtrA/VtrC, we identify a fast-evolving superfamily of co-component systems in enteric bacteria. Accurate machine learning-based fold predictions for the candidate co-components support their homology in the twilight zone of rapidly evolving sequence and provide mechanistic hypotheses about previously unrecognized lipid-sensing functions. Significance statement: Using the domain and operon organization of VtrA/VtrC, combined with fold predictions, we identify new co-component signal transduction systems in enteric bacteria that likely regulate virulence. We observe that the heterodimeric VtrA/VtrC periplasmic bile acid receptor controlling Vibrio parahaemolyticus T3SS2 is a distant homolog of the ToxR/ToxS master regulator of virulence and has evolved beyond confident sequence recognition. Exploiting the newly developed machine learning methods for structure prediction, we observe a VtrC-like lipocalin fold for both the ToxS periplasmic domain and for other detected periplasmic sensor components. This structure prediction supports the divergent evolution of VtrA/VtrC-like co-component signal transduction systems and suggests a role for lipid sensing in regulating virulence in enteric bacteria.

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Metadata

Authors
Kinch, L. N., Cong, Q., Jaishankar, J., & Orth, K.
Affiliations
  • Howard Hughes Medical Institute (US)
  • The University of Texas Southwestern Medical Center (US)
Corresponding author
Orth, Kim
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
openRxiv
Published
2022-04-08
Volume
119
Issue
24
Pages
e2203176119-e2203176119
ISSN
0027-8424 (ISSN-L)
DOI
10.1101/2022.04.08.487670
PMC
PMC9214523
OpenAlex
W4281941988
Cited by
25
References
1
Citations by year
2026: 4 · 2025: 5 · 2024: 5 · 2023: 8 · 2022: 3
FWCI
3.17
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Welch Foundation (I‐1561)
  • Once Upon A Time Foundation
  • Southwestern Medical Foundation
  • National Institutes of Health
  • National Institute of General Medical Sciences (R35GM134945, R01GM115188)
  • Center for Scientific Review (R01 GM115188)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
  • Life Sciences › Immunology and Microbiology › Microbiology › Vibrio bacteria research studies
Keywords
two-component systems, one-component systems, phosphorelay, Vibrio parahaemolyticus, type III secretion system, enteric bacteria, virulence regulation, lipid sensing, protein fold prediction, operon organization
MeSH terms
Type III Secretion Systems, Bacterial Proteins, Bile Acids and Salts, DNA-Binding Proteins, Membrane Proteins, Transcription Factors, Vibrio parahaemolyticus, Virulence, Signal Transduction, Gene Expression Regulation, Bacterial, Genomic Islands, Protein Multimerization

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