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Harnessing CRISPR-Cas technology for sustainable antibiotic resistance markers

Project description

Sustainable antibiotic resistance management

Antibiotic resistance spreads through plasmids in labs and industry. To address this, strategies such as non-antibiotic selection and strict containment are needed, but they require specialised personnel. A recent approach proposes using markers that silence natural bacterial genes, allowing low antibiotic concentrations to kill resistant bacteria and reducing the risk of gene transfer to pathogens. The ERC-funded SENSIBLIOTICS project aims to create an easy-to-use marker using the CRISPR-Cas system to down-regulate genes related to antibiotic sensitivity and confer resistance. It will validate its effectiveness across bacterial strains for various applications, clarify intellectual property, and foster collaborations. The project seeks to transform bacterial maintenance processes and reduce costs related to antibiotic resistance management.

Objective

The active spread of antibiotic resistance in laboratories and industry often occurs through the use of plasmids, which transfer resistance genes between bacteria. To mitigate this, strategies such as non-antibiotic selection methods, stringent containment protocols, and plasmid designs that minimize horizontal gene transfer have been proposed. However, these strategies often involve complex methodologies and require highly trained personnel. Recently, our ERC Consolidator results opened the path for a novel approach to develop antibiotic resistance markers for bacterial selection based on silencing naturally occurring bacterial genes without introducing new resistance elements. Unlike most resistance markers, it lacks a mechanism for degrading antibiotics. Therefore, a low concentration of antibiotics is sufficient to kill bacteria harboring it, minimizing the risk of transferring resistance genes to pathogens.
To generate this easy-to-use marker, we will use the CRISPR-Cas system to randomly silence or down-regulate specific genes, including essential ones. We will identify guides that down-regulate genes associated with antibiotic sensitivity and then use these guides along with a Cas-silencer to confer antibiotic resistance. This proof-of-concept will validate the marker's effectiveness across bacterial strains for laboratory and industrial applications, clarify intellectual property positions, and establish industrial collaborations. With a team led by Prof. Qimron, an expert in bacterial defense systems, we anticipate a transformative impact on bacterial selection and maintenance processes. This novel marker has potential applications in medical research, biotechnology, microbiome manipulation, and industrial production. Its deployment will significantly reduce costs associated with antibiotic resistance management and treatment, contributing to a sustainable approach to tackling antibiotic resistance.

Fields of science (EuroSciVoc)

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

(opens in new window) ERC-2025-POC

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Host institution

TEL AVIV UNIVERSITY
Net EU contribution
€ 150 000,00
Total cost
No data

Beneficiaries (1)