Synthetic Biology-Based Approaches to Investigate 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 pathogenesis and developing effective therapies. This review underscores the potential of synthetic biology in elucidating host–pathogen interactions and facilitating the creation of advanced diagnostic tools and targeted therapies to combat MDR infections. We first explore CRISPR-based strategies that modulate essential gene expression, providing insights into the molecular mechanisms underlying host–pathogen interactions. Next, we discuss engineered microbial synthetic circuits for rapid pathogen detection by identifying molecular signatures involved in interspecies communication and facilitating swift pathogen elimination. Additionally, we explore 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 application 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 physiology and pathophysiology, thereby enabling more accurate disease modeling, drug testing, and the development of personalized medicine. Collectively, these synthetic biology tools provide transformative insights into the molecular mechanisms of host–pathogen interactions, advancing the development of precise diagnostic and therapeutic strategies against MDR infections.