Rima Zein Eddine

Project title:  DNA repair and resistance evolution in Mycobacterium tuberculosis

Host Institution: École Polytechnique (l’X)

Host Supervisor: Dr. Hannu Myllykallio

Co-host Institution: Technical University of Denmark (DTU)

Co-host Supervisor: Prof. Lars Jelsbak

Summary project: The social and economic burden of the infectious disease ”Tuberculosis” (TB) caused by the pathogen Mycobacterium tuberculosis (MTB), is very high with the increasing impact of antibiotic resistance. In this species, resistance relies on the acquisition of genomic mutations in drugs targets. Whereas the role of mutator genotypes in resistance emergence is well-acknowledged in several bacterial pathogens, the frequency of mutator genotypes among clinical MTB isolates and their effective contribution to the emergence of antimicrobial resistance (AMR) remains unknown. Our overall goal is to provide novel information on the development of genetic diversity in MTB, especially in DNA repair system genes, and link it to the frequent emergence of epidemic multi-resistant strains. Importantly, our goals include detailed structural characterization of the effects of those mutations as exemplified on several important protein systems. A second important goal of this project is to contribute to the development of new antibacterial strategies based on our very recent discoveries. It is in line with current studies in the field but it covers an understudied area of bacterial AMR. To study the major components that affect the diversification process in MTB clinical strains is a novel approach to an old need of the Global Antibiotic Resistance Market. Beyond academia and related research fields, this project is focusing on the second deadly infectious pathogen after COVID and has the potential to impact, in the long-term, the health sector and ‘quality of life’/’Lifelong Health worldwide.