Targeting antimicrobial resistance genes using phage-delivered CRISPR- Cas

• Grant number: 24/00854-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2024
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Ana Cristina Gales
• Grantee: Mustapha Goni Abatcha
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 21/10599-3 - The Antimicrobial Resistance Institute of São Paulo (The Aries Project), AP.CEPID

Abstract

We have witnessed a dramatic increase in infections caused by multidrug- resistant (MDR) bacteria in the last decades. Recently, A. baumannii, P. aeruginosa, and Enterobacterales resistant to carbapenems were elected by WHO as critical pathogens to guide research and development of new antimicrobials [Tacconelli et al., 2018]. The use of new therapeutic strategies to control the emergence and spread of MDR bacteria has been encouraged. In the nosocomial setting, controlling the spread of MDR bacteria is crucial to prevent further infections. Based on that, new therapies and drugs has been researched and developed. In the last years, the CRISPR-Cas system gained attention as a very useful tool to be applied in many researches areas. Among them, to tackle antimicrobial resistance (AMR) by targeting specific MDR pathogens [Gholizadeh et al., 2020]. Furthermore, the CRISPR-Cas system can be delivered by bacteriophages, which is very interesting since bacteriophages are specie and clone specific, and CRISPR-Cas is a tool to edit specific genome regions [Cobb et al., 2019; Fage et al., 2021; Park et al., 2017]. Thus, putting these two techniques together, good results to combat AMR could be achieved. Recent studies obtained success by applying phage-based CRISPR-Cas system to combat AMR and persistent infection, like Clostridium difficile. Based on that, in the present project we propose targeting antimicrobial resistance genes, as carbapenemases, in Enterobacterales applying phage-based CRISPR-Cas system delivery.