Synthetic Biology-Based Approaches to Probe Host-Pathogen Interactions

The increasing prevalence of multi-drug-resistant (MDR) bacterial pathogens presents a critical global health threat, highlighting the urgent need for innovative approaches to understanding bacterial patho-genesis and developing effective therapies. This review explores the potential of synthetic biology as a promising tool for investigating host-pathogen interactions and offering alternative therapeutic solu-tions for MDR infections. We first examine the progress of CRISPR-based strategies that have enabled modulation of essential gene expression, providing insights into the molecular mechanisms underly-ing host-pathogen interactions. We then discuss the use of engineered microbial synthetic circuits for rapid pathogen detection, which identify molecular signatures involved in interspecies communica-tion and facilitate swift pathogen elimination. Additionally, we explore the potential of Phage Therapy (PT), which leverages bacteriophages to selectively target and eliminate specific bacterial pathogens, presenting a targeted and promising approach to combat MDR infections. Finally, we review the appli-cation of Organ-On-A-Chip (OOAC) technology, which overcomes the limitations of animal models in predicting human immune responses by using microfluidic devices that simulate organ-level physi-ology and pathophysiology, thereby enabling more accurate disease modeling, drug testing, and the development of personalized medicine.