ClbR Is the Key Transcriptional Activator of Colibactin Gene Expression in Escherichia coli

Author:

Wallenstein Alexander1,Rehm Nadine12,Brinkmann Marina1,Selle Martina3,Bossuet-Greif Nadège4,Sauer Daniel5,Bunk Boyke67,Spröer Cathrin6,Wami Haleluya Tesfaye1,Homburg Stefan3,von Bünau Rudolf8,König Simone9,Nougayrède Jean-Philippe4,Overmann Jörg67,Oswald Eric4,Müller Rolf5,Dobrindt Ulrich123ORCID

Affiliation:

1. Institute of Hygiene, University of Münster, Münster, Germany

2. Interdisciplinary Center for Clinical Research, Medical Faculty, University of Münster, Münster, Germany

3. Institute of Molecular Infection Biology, University of Würzburg, Würzburg, Germany

4. IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, Toulouse, France

5. Department of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland, Helmholtz Center for Infection Research, Saarland University, Saarbrücken, Germany

6. Leibniz Institute DSMZ—German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany

7. DZIF—German Center for Infection Research, Hannover-Braunschweig Partner Site, Braunschweig, Germany

8. Pharma Zentrale GmbH, Herdecke, Germany

9. Core Unit Proteomics, Interdisciplinary Center for Clinical Research, Medical Faculty, University of Münster, Münster, Germany

Abstract

The nonribosomal peptide/polyketide hybrid colibactin can be considered a bacterial virulence factor involved in extraintestinal infection and also a procarcinogen. Nevertheless, and despite its genotoxic effect, colibactin expression can also inhibit bacterial or tumor growth and correlates with probiotic anti-inflammatory and analgesic properties. Although the biological function of this natural compound has been studied extensively, our understanding of the regulation of colibactin expression is still far from complete. We investigated in detail the role of regulatory elements involved in colibactin expression and in the growth conditions that promote colibactin expression. In this way, our data shed light on the regulatory mechanisms involved in colibactin expression and may support the expression and purification of this interesting nonribosomal peptide/polyketide hybrid for further molecular characterization.

Funder

Interdisciplinary Center for Clinical Research, Medical Faculty Münster

Deutsche Forschungsgemeinschaft

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology

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