Research Projects

Commensal bacteria in the gut interact symbiotically with the hosts and play a major role in gut health and overall fitness (1,2). These effects are exhibited by modulating several host functions, including development, metabolism, and immunity (3,4). In contrast, common gut pathogens have several intrinsic mechanisms for subverting host defence, facilitating host pathogenicity, and enduring exposure to various environmental stressors (5). Pathogenic gut microbiota often utilizes highly specialized secretion systems for self-survival, promoting subsequent disease progression and competitive advantages (6,7). Among them, the bacterial Type VI Secretion System (T6SS) has been claimed to be functionally versatile and can secrete a range of effector molecules to modulate the intestinal microenvironment (8,9). C. jejuni-T6SS resembles an inverted phage-like puncturing device composed of 13 core proteins, TssA to M, a group of tightly clustered genes, including Valine-Glycine Repeat G (VgrG or TssI) and Hemolysin Co-regulated Protein (Hcp or TssD) are hallmarks of functional T6SS (10-12). The bacterial T6SS functions via dynamic cycles of assembly, contraction, and disassembly, attacking both prokaryotic and eukaryotic cells in a contact-dependent manner (13-15). Despite the competitive fitness advantage of the T6SS, its functionality can depend on the physico-chemical composition of the gut, such as pH, bile salt concentration, and the presence of other antimicrobial components6. How such stressors affect the T6SS activity and the ultimate fate of T6SS-harboring pathogens is an intriguing and open question. In line with the question, using Campylobacter jejuni (C. jejuni) as a model gut pathogen and poultry as the primary host, we aim to understand: 1. How does T6SS-positive C. jejuni exhibit enteric commensalism in the chicken gut, where many other bacteria coexist, including T6SS-negative C. jejuni? 2. Can environmental factors, such as the physicochemical compositions of the gut or other molecules from other resident bacteria, including antibiotics, affect the T6SS-dependent intraspecies and interspecies interactions? 3. As a dynamic and target-driven functional unit of C. jejuni, does the bidirectional contraction of T6SS allow two-way effector functions? 4. Finally, can we exploit the unique attributes of target-driven T6SS functionality towards persuading the self-destruction of C. jejuni in chickens?