The cell wall lipoprotein CD1687 acts as a DNA binding protein during deoxycholate-induced biofilm formation in Clostridioides difficile.


Journal

NPJ biofilms and microbiomes
ISSN: 2055-5008
Titre abrégé: NPJ Biofilms Microbiomes
Pays: United States
ID NLM: 101666944

Informations de publication

Date de publication:
11 05 2023
Historique:
received: 06 12 2022
accepted: 27 04 2023
medline: 15 5 2023
pubmed: 12 5 2023
entrez: 11 5 2023
Statut: epublish

Résumé

The ability of bacterial pathogens to establish recurrent and persistent infections is frequently associated with their ability to form biofilms. Clostridioides difficile infections have a high rate of recurrence and relapses and it is hypothesized that biofilms are involved in its pathogenicity and persistence. Biofilm formation by C. difficile is still poorly understood. It has been shown that specific molecules such as deoxycholate (DCA) or metronidazole induce biofilm formation, but the mechanisms involved remain elusive. In this study, we describe the role of the C. difficile lipoprotein CD1687 during DCA-induced biofilm formation. We showed that the expression of CD1687, which is part of an operon within the CD1685-CD1689 gene cluster, is controlled by multiple transcription starting sites and some are induced in response to DCA. Only CD1687 is required for biofilm formation and the overexpression of CD1687 is sufficient to induce biofilm formation. Using RNAseq analysis, we showed that CD1687 affects the expression of transporters and metabolic pathways and we identified several potential binding partners by pull-down assay, including transport-associated extracellular proteins. We then demonstrated that CD1687 is surface exposed in C. difficile, and that this localization is required for DCA-induced biofilm formation. Given this localization and the fact that C. difficile forms eDNA-rich biofilms, we confirmed that CD1687 binds DNA in a non-specific manner. We thus hypothesize that CD1687 is a component of the downstream response to DCA leading to biofilm formation by promoting interaction between the cells and the biofilm matrix by binding eDNA.

Identifiants

pubmed: 37169797
doi: 10.1038/s41522-023-00393-5
pii: 10.1038/s41522-023-00393-5
pmc: PMC10175255
doi:

Substances chimiques

DNA-Binding Proteins 0
Lipoproteins 0
Deoxycholic Acid 005990WHZZ

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

24

Informations de copyright

© 2023. The Author(s).

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Auteurs

Emile Auria (E)

Institut Pasteur, Université Paris-Cité, UMR-CNRS 6047, Laboratoire Pathogenèse des Bactéries Anaérobies, F-75015, Paris, France.

Lise Hunault (L)

Institut Pasteur, Université Paris-Cité, INSERM UMR1222, Unit of Antibodies in Therapy and Pathology, Paris, France.
Sorbonne Université, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), F-75013, Paris, France.

Patrick England (P)

Plateforme de Biophysique Moléculaire, Institut Pasteur, CNRS UMR3528, Paris, France.

Marc Monot (M)

Plateforme Technologique Biomics, Institut Pasteur, Paris, France.

Juliana Pipoli Da Fonseca (J)

Plateforme Technologique Biomics, Institut Pasteur, Paris, France.

Mariette Matondo (M)

Plateforme Proteomic, Institut Pasteur, Paris, France.

Magalie Duchateau (M)

Plateforme Proteomic, Institut Pasteur, Paris, France.

Yannick D N Tremblay (YDN)

Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada.

Bruno Dupuy (B)

Institut Pasteur, Université Paris-Cité, UMR-CNRS 6047, Laboratoire Pathogenèse des Bactéries Anaérobies, F-75015, Paris, France. bruno.dupuy@pasteur.fr.

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Classifications MeSH