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Quorum sensing as a tool to detect and target pro-oncogenic microbial biofilms associated with right-sided colorectal cancer

Project description

Targeting pro-oncogenic biofilms in the colon

Colorectal cancer (CRC) development is linked to specific pathogenic bacteria known to disrupt gut epithelial integration and to cause inflammation. These bacteria employ a communication process known as quorum sensing to coordinate their behaviour and form invasive biofilms. With the support of the Marie Skłodowska-Curie Actions programme, the BIFCOLC-QS project aims to harness the concept of quorum sensing to design an innovative approach for early CRC detection. Researchers propose to engineer a probiotic strain that can sense specific molecules secreted by CRC-causing pathogenic bacteria. The strain will express an enzyme that can disrupt these biofilms and kill the pathogenic bacteria, offering a novel strategy for early CRC treatment.

Objective

Colorectal cancer (CRC) development and progression have been linked to the presence of pro-oncogenic bacterial strains in the intestine, such as Fusobacterium nucleatum, pks+ Escherichia coli and enterotoxigenic Bacteroides fragilis. These pathogenic bacteria produce toxins that can disrupt gut epithelial integrity resulting in heightened pro-inflammatory response, enhanced DNA mutations, and increased cell proliferation, which can eventually lead to adenoma formation. In addition, these bacterial pathogens show increased genotoxicity by forming invasive polymicrobial biofilms, thereby resulting in CRC development. Recently it has been reported that anatomical location plays a crucial role in CRC development, progression, microbial colonization, response to therapies and disease outcome. Indeed, right-sided CRC is generally associated with pro-oncogenic bacterial biofilms and is known to have an overall worse prognosis compared to left-sided CRC. Pathogenic bacteria use quorum sensing (QS) machinery in the gut for their communication, which is essential for biofilm formation. We aim to develop an intervention strategy employing QS machinery to engineer a probiotic bacterial strain with sensing and killing properties to detect and target these pro-oncogenic polymicrobial biofilms. The sensor device will detect autoinducers produced by pathogenic bacteria on encountering their biofilms, activating the killing device. The killing device expresses a biofilm degrading enzyme, Dispersin B, which will disrupt these biofilms and eventually kill the pathogenic bacteria residing in these biofilms by the type VI secretion system. These polymicrobial biofilms can act as a marker of CRC and help to understand the role of CRC-associated pathogenic bacteria in CRC development, which can eventually serve as a basis for developing future strategies for the diagnosis and treatment of CRC and other intestinal disorders associated with biofilms formed by pathogenic bacteria.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2022-PF-01

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Coordinator

EUROPEAN MOLECULAR BIOLOGY LABORATORY
Net EU contribution
€ 173 847,36
Address
Meyerhofstrasse 1
69117 Heidelberg
Germany
Region
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Research Organisations
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Total cost
No data