Molecular Assembly and Host Targeting Mechanisms of the Type III Secretion System
The Type III Secretion System (T3SS) is a complex molecular machine essential for bacterial virulence, requiring precise assembly and targeting mechanisms for effective pathogen-host interaction. Our research aims to elucidate both the assembly process of the T3SS, which involves approximately 20 different proteins expressed under specific host-like conditions (temperature, pH, and physiological osmolarity), and the subsequent host membrane targeting mediated by the translocon complex. This translocon complex, composed of 2-3 proteins, represents the critical interface between the pathogen and host cell, facilitating effector protein transport across the plasma membrane. By investigating the interplay between T3SS assembly conditions and translocon formation, along with the mechanisms governing host membrane interaction and pore formation, we seek to develop comprehensive therapeutic strategies. Understanding these fundamental processes will enable rational modification and inhibition of this widely conserved virulence machinery employed by Gram-negative bacterial pathogens, leading to novel applications in both biotechnology and medicine. Our integrated approach addresses the complete pathway from initial T3SS assembly to final host cell interaction, providing multiple potential intervention points for therapeutic development.
Diet and bacterial virulence
Our lab explores how dietary components influence bacterial pathogenesis and virulence mechanisms. Recent evidence suggests that the nutrients in our diet can significantly impact bacterial behavior and their ability to cause disease. Using advanced molecular techniques, we investigate how specific dietary compounds modulate bacterial gene expression, particularly focusing on virulence factors like the T3SS. We examine how different nutritional environments affect bacterial metabolism, colonization abilities, and host-pathogen interactions. Understanding these diet-pathogen interactions provides new insights into how nutrition affects infection outcomes and opens novel therapeutic approaches that could exploit dietary interventions to combat bacterial infections.
Engineering Bacterial Secretion Systems for Oral administration of Protein Therapeutics
Our lab is pioneering an innovative approach to one of the most significant challenges in modern medicine: the oral delivery of protein-based drugs. While these therapeutics hold immense medical potential, their oral administration has been historically limited by protein degradation in the gastrointestinal environment and prohibitively expensive delivery systems. We are developing a groundbreaking solution by harnessing bacteria with secretion systems, particularly Type III and Type V secretion systems, as natural protein delivery platforms. These sophisticated molecular machines, which bacteria have evolved to transport proteins across biological barriers, offer a unique opportunity to create efficient and cost-effective oral administration systems. By engineering these bacterial secretion systems, we aim to develop a versatile platform that can protect and deliver therapeutic proteins directly to the lumen of the intestine. This approach could revolutionize the administration of protein-based medications, making them more accessible, convenient, and affordable for patients while opening new possibilities for treating various diseases that currently require injectable therapies.
Polymicrobial Infections: Beyond Single-Pathogen Disease
Our lab investigates the complex dynamics of multi-pathogen infections, challenging the traditional one-microbe, one-disease paradigm that has dominated bacterial infection research for over a century. Modern molecular diagnostics reveal that polymicrobial infections are remarkably common, particularly in diarrheal illnesses, where they account for 30-50% of cases. Using advanced co-pathogen infection models, we study how different bacterial pathogens interact with each other and with commensal bacteria within the host environment. Our research specifically focuses on understanding the molecular mechanisms and synergistic relationships that emerge during these complex infections. This work is revolutionizing our understanding of infectious diseases and has significant implications for developing more effective diagnostic tools and therapeutic strategies that address the reality of polymicrobial infections.
