Abstract:
Antimicrobial resistance (AMR) stands as one of the most critical challenges of our time. Indeed, The World health organization ranked AMR among the major alarming global threats to medicine and public health. The rapid evolution and dissemination of resistant pathogens demand urgent and innovative solutions. Among the most promising approaches is Synthetic Biology, a field that merges engineering principles with biological systems to design entirely new biological systems or re-engineering existing ones to introduce novel functions and capabilities.

We explored two synergistic strategies to address AMR. The first approach involves engineering bacteria to disrupt pathogen communication systems, specifically Quorum Sensing (QS). QS is a cell-to-cell communication mechanism that enables bacteria to coordinate community-level resistance mechanisms, including biofilm formation and virulence. 

The second approach focuses on delivering a CRISPR interference (CRISPRi) system into target pathogens. This system specifically inhibits AMR-associated genes, thereby restoring bacterial sensitivity to antibiotics. 

Control Theory played a pivotal role in this work, providing a framework to model, analyze, and manipulate biological systems. It offered valuable insights into their structural properties and guided the design and optimization of the proposed synthetic biology strategies.