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Distinct PlzC mechanisms integrate chemotaxis and c-di-GMP signaling to regulate Vibrio cholerae motility and biofilm formation

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Title: Distinct PlzC mechanisms integrate chemotaxis and c-di-GMP signaling to regulate Vibrio cholerae motility and biofilm formation
Authors: Park, Jin Hwan, Kennedy, Emily N., Tripathi, Sarvind, Romp, Avery B., Rubin, Seth M., Bourret, Robert B., Yildiz, Fitnat H.
Source: Proceedings of the National Academy of Sciences of the United States of America, 123(2)
Publisher Information: National Academy of Sciences
Publication Year: 2026
Collection: Carolina Digital Repository (UNC - University of North Carolina)
Subject Terms: Phase transitions, Full-length 16S rRNA amplicon sequencing, Servicios de Salud Dental, renal replacement therapy, Organic crystals, leptomeningeal carcinomatosis, health services research, Emergency department, SRHR, Xpert® MTB/RIF ultra, aging, Resource-limited, Skeletal muscle, adaptive treatment assignment, Health, Anti-inflammatory activity, Meio Ambiente e Saúde Pública, neural dynamics model, Chronic disease, liver transplantation, prognostic factors, gastric biopsy, preference for dying at home, incidence, Venetoclax, dopamine receptor D2 (DRD2), 675 nm laser, pathogenesis, Youth, group dynamics
Description: Significance Bacterial motility and biofilm formation critically facilitate adaptation and survival and are regulated by the second messenger c-di-GMP. Vibrio cholerae PilZ domain proteins are c-di-GMP effectors, but the mechanisms by which they govern cellular processes are poorly understood. This study identifies PlzC as a critical integrator of motility and biofilm development via multiple pathways. PlzC promotes motility by regulating CheX, a CheY-3 phosphatase that impacts migration direction. While CheX modulates directional changes through CheY-3 dephosphorylation, PlzC more broadly impacts biofilm maturation, indicating PlzC has a dual regulatory role that targets different stages leading to biofilm formation. PlzC is a key link between chemotaxis and c-di-GMP signaling, providing insight into bacterial adaptability and potentially serving as a target for therapeutic approaches. ; Bacterial motility and biofilm formation are essential for the adaptation and survival of Vibrio cholerae, the causative agent of cholera. In many bacterial species, the second messenger c-di-GMP regulates these processes through PilZ domain proteins, however the downstream mechanisms have remained poorly defined. Here, we identify the PilZ domain protein PlzC as a key positive regulator of motility and biofilm formation through distinct mechanisms. A suppressor screen for mutants restoring ΔplzC migration identified downstream regulators, including CheX, a CheY-3 phosphatase. Genetic and phenotypic analyses revealed that PlzC promotes motility by modulating CheX, thereby influencing the frequency of direction changes during swimming. Notably, the role of PlzC in motility regulation is independent of CheZ, another CheY-3 phosphatase, demonstrating that among the two CheY-3 phosphatases, only CheX is under PlzC control. This distinction suggests that CheY-3-P levels are regulated by at least two separate signaling pathways, one of which operates through PlzC. Despite its function in motility, CheX is not required for ...
Document Type: article in journal/newspaper
Language: unknown
Relation: https://cdr.lib.unc.edu/downloads/k0698r282?file=thumbnail; https://cdr.lib.unc.edu/downloads/k0698r282
DOI: 10.17615/t3jb-g473
Availability: https://doi.org/10.17615/t3jb-g473
https://cdr.lib.unc.edu/downloads/k0698r282?file=thumbnail
https://cdr.lib.unc.edu/downloads/k0698r282
Rights: http://rightsstatements.org/vocab/InC/1.0/ ; http://creativecommons.org/licenses/by-nc-nd/4.0/
Accession Number: edsbas.4AFA4419
Database: BASE
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  – Url: https://doi.org/10.17615/t3jb-g473#
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PubType: Academic Journal
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  Data: Distinct PlzC mechanisms integrate chemotaxis and c-di-GMP signaling to regulate Vibrio cholerae motility and biofilm formation
– Name: Author
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  Data: <searchLink fieldCode="AR" term="%22Park%2C+Jin+Hwan%22">Park, Jin Hwan</searchLink><br /><searchLink fieldCode="AR" term="%22Kennedy%2C+Emily+N%2E%22">Kennedy, Emily N.</searchLink><br /><searchLink fieldCode="AR" term="%22Tripathi%2C+Sarvind%22">Tripathi, Sarvind</searchLink><br /><searchLink fieldCode="AR" term="%22Romp%2C+Avery+B%2E%22">Romp, Avery B.</searchLink><br /><searchLink fieldCode="AR" term="%22Rubin%2C+Seth+M%2E%22">Rubin, Seth M.</searchLink><br /><searchLink fieldCode="AR" term="%22Bourret%2C+Robert+B%2E%22">Bourret, Robert B.</searchLink><br /><searchLink fieldCode="AR" term="%22Yildiz%2C+Fitnat+H%2E%22">Yildiz, Fitnat H.</searchLink>
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  Data: Proceedings of the National Academy of Sciences of the United States of America, 123(2)
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  Data: National Academy of Sciences
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  Data: 2026
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  Data: Carolina Digital Repository (UNC - University of North Carolina)
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  Data: <searchLink fieldCode="DE" term="%22Phase+transitions%22">Phase transitions</searchLink><br /><searchLink fieldCode="DE" term="%22Full-length+16S+rRNA+amplicon+sequencing%22">Full-length 16S rRNA amplicon sequencing</searchLink><br /><searchLink fieldCode="DE" term="%22Servicios+de+Salud+Dental%22">Servicios de Salud Dental</searchLink><br /><searchLink fieldCode="DE" term="%22renal+replacement+therapy%22">renal replacement therapy</searchLink><br /><searchLink fieldCode="DE" term="%22Organic+crystals%22">Organic crystals</searchLink><br /><searchLink fieldCode="DE" term="%22leptomeningeal+carcinomatosis%22">leptomeningeal carcinomatosis</searchLink><br /><searchLink fieldCode="DE" term="%22health+services+research%22">health services research</searchLink><br /><searchLink fieldCode="DE" term="%22Emergency+department%22">Emergency department</searchLink><br /><searchLink fieldCode="DE" term="%22SRHR%22">SRHR</searchLink><br /><searchLink fieldCode="DE" term="%22Xpert®+MTB%2FRIF+ultra%22">Xpert® MTB/RIF ultra</searchLink><br /><searchLink fieldCode="DE" term="%22aging%22">aging</searchLink><br /><searchLink fieldCode="DE" term="%22Resource-limited%22">Resource-limited</searchLink><br /><searchLink fieldCode="DE" term="%22Skeletal+muscle%22">Skeletal muscle</searchLink><br /><searchLink fieldCode="DE" term="%22adaptive+treatment+assignment%22">adaptive treatment assignment</searchLink><br /><searchLink fieldCode="DE" term="%22Health%22">Health</searchLink><br /><searchLink fieldCode="DE" term="%22Anti-inflammatory+activity%22">Anti-inflammatory activity</searchLink><br /><searchLink fieldCode="DE" term="%22Meio+Ambiente+e+Saúde+Pública%22">Meio Ambiente e Saúde Pública</searchLink><br /><searchLink fieldCode="DE" term="%22neural+dynamics+model%22">neural dynamics model</searchLink><br /><searchLink fieldCode="DE" term="%22Chronic+disease%22">Chronic disease</searchLink><br /><searchLink fieldCode="DE" term="%22liver+transplantation%22">liver transplantation</searchLink><br /><searchLink fieldCode="DE" term="%22prognostic+factors%22">prognostic factors</searchLink><br /><searchLink fieldCode="DE" term="%22gastric+biopsy%22">gastric biopsy</searchLink><br /><searchLink fieldCode="DE" term="%22preference+for+dying+at+home%22">preference for dying at home</searchLink><br /><searchLink fieldCode="DE" term="%22incidence%22">incidence</searchLink><br /><searchLink fieldCode="DE" term="%22Venetoclax%22">Venetoclax</searchLink><br /><searchLink fieldCode="DE" term="%22dopamine+receptor+D2+%28DRD2%29%22">dopamine receptor D2 (DRD2)</searchLink><br /><searchLink fieldCode="DE" term="%22675+nm+laser%22">675 nm laser</searchLink><br /><searchLink fieldCode="DE" term="%22pathogenesis%22">pathogenesis</searchLink><br /><searchLink fieldCode="DE" term="%22Youth%22">Youth</searchLink><br /><searchLink fieldCode="DE" term="%22group+dynamics%22">group dynamics</searchLink>
– Name: Abstract
  Label: Description
  Group: Ab
  Data: Significance Bacterial motility and biofilm formation critically facilitate adaptation and survival and are regulated by the second messenger c-di-GMP. Vibrio cholerae PilZ domain proteins are c-di-GMP effectors, but the mechanisms by which they govern cellular processes are poorly understood. This study identifies PlzC as a critical integrator of motility and biofilm development via multiple pathways. PlzC promotes motility by regulating CheX, a CheY-3 phosphatase that impacts migration direction. While CheX modulates directional changes through CheY-3 dephosphorylation, PlzC more broadly impacts biofilm maturation, indicating PlzC has a dual regulatory role that targets different stages leading to biofilm formation. PlzC is a key link between chemotaxis and c-di-GMP signaling, providing insight into bacterial adaptability and potentially serving as a target for therapeutic approaches. ; Bacterial motility and biofilm formation are essential for the adaptation and survival of Vibrio cholerae, the causative agent of cholera. In many bacterial species, the second messenger c-di-GMP regulates these processes through PilZ domain proteins, however the downstream mechanisms have remained poorly defined. Here, we identify the PilZ domain protein PlzC as a key positive regulator of motility and biofilm formation through distinct mechanisms. A suppressor screen for mutants restoring ΔplzC migration identified downstream regulators, including CheX, a CheY-3 phosphatase. Genetic and phenotypic analyses revealed that PlzC promotes motility by modulating CheX, thereby influencing the frequency of direction changes during swimming. Notably, the role of PlzC in motility regulation is independent of CheZ, another CheY-3 phosphatase, demonstrating that among the two CheY-3 phosphatases, only CheX is under PlzC control. This distinction suggests that CheY-3-P levels are regulated by at least two separate signaling pathways, one of which operates through PlzC. Despite its function in motility, CheX is not required for ...
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  Data: 10.17615/t3jb-g473
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  Data: https://doi.org/10.17615/t3jb-g473<br />https://cdr.lib.unc.edu/downloads/k0698r282?file=thumbnail<br />https://cdr.lib.unc.edu/downloads/k0698r282
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  Data: http://rightsstatements.org/vocab/InC/1.0/ ; http://creativecommons.org/licenses/by-nc-nd/4.0/
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  Data: edsbas.4AFA4419
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      – Type: doi
        Value: 10.17615/t3jb-g473
    Languages:
      – Text: unknown
    Subjects:
      – SubjectFull: Phase transitions
        Type: general
      – SubjectFull: Full-length 16S rRNA amplicon sequencing
        Type: general
      – SubjectFull: Servicios de Salud Dental
        Type: general
      – SubjectFull: renal replacement therapy
        Type: general
      – SubjectFull: Organic crystals
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      – SubjectFull: leptomeningeal carcinomatosis
        Type: general
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      – SubjectFull: SRHR
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      – SubjectFull: Xpert® MTB/RIF ultra
        Type: general
      – SubjectFull: aging
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      – SubjectFull: Resource-limited
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      – SubjectFull: Skeletal muscle
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      – SubjectFull: adaptive treatment assignment
        Type: general
      – SubjectFull: Health
        Type: general
      – SubjectFull: Anti-inflammatory activity
        Type: general
      – SubjectFull: Meio Ambiente e Saúde Pública
        Type: general
      – SubjectFull: neural dynamics model
        Type: general
      – SubjectFull: Chronic disease
        Type: general
      – SubjectFull: liver transplantation
        Type: general
      – SubjectFull: prognostic factors
        Type: general
      – SubjectFull: gastric biopsy
        Type: general
      – SubjectFull: preference for dying at home
        Type: general
      – SubjectFull: incidence
        Type: general
      – SubjectFull: Venetoclax
        Type: general
      – SubjectFull: dopamine receptor D2 (DRD2)
        Type: general
      – SubjectFull: 675 nm laser
        Type: general
      – SubjectFull: pathogenesis
        Type: general
      – SubjectFull: Youth
        Type: general
      – SubjectFull: group dynamics
        Type: general
    Titles:
      – TitleFull: Distinct PlzC mechanisms integrate chemotaxis and c-di-GMP signaling to regulate Vibrio cholerae motility and biofilm formation
        Type: main
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            NameFull: Park, Jin Hwan
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              Type: published
              Y: 2026
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            – TitleFull: Proceedings of the National Academy of Sciences of the United States of America, 123(2
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