Harnessing CRISPR-Cas technology for sustainable antibiotic resistance markers

Descripción del proyecto

Gestión sostenible de la resistencia a los antibióticos

La resistencia a los antibióticos se propaga a través de plásmidos en los laboratorios y la industria. Para hacer frente a esto, se necesitan estrategias como la selección sin antibióticos y la contención estricta, pero requieren personal especializado. Un planteamiento reciente propone utilizar marcadores que silencien genes bacterianos naturales, permitiendo que bajas concentraciones de antibióticos acaben con las bacterias resistentes y reduciendo el riesgo de transferencia de genes a patógenos. El proyecto SENSIBLIOTICS, financiado por el Consejo Europeo de Investigación, pretende crear un marcador fácil de usar que utilice el sistema CRISPR-Cas para regular a la baja genes relacionados con la sensibilidad a los antibióticos y conferir resistencia. Asimismo, validará su eficacia entre cepas bacterianas para diversas aplicaciones, aclarará la propiedad intelectual y fomentará las colaboraciones. El proyecto pretende transformar los procesos de mantenimiento bacteriano y reducir los costes relacionados con la gestión de la resistencia a los antibióticos.

Objetivo

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.