Molecular Basis and Regulatory Mechanisms of Bacterial Interspecies and Intercellular Interactions

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Microbes almost always exist in microbial communities. Intercellular interactions between the members of a community affect an individual microbe's gene expression, activities and survival, and shape the structure and function of the microbial community. To comprehend the bacterial life process and understand microbial communities such as biofilms and human microbiota, it is essential to know how bacterial cells interact with their neighbouring cells and how they regulate their genes and behaviours in response to such interactions. The long-term goal of my research program is to understand the molecular basis and regulatory pathways of bacterial interspecies and intercellular interactions. My research focuses on Pseudomonas aeruginosa, a ubiquitous Gram-negative bacterium that causes serious infections in plants, animals and humans. P. aeruginosa is a paradigmatic model microorganism for study of biofilms and bacterial cell-cell interaction including quorum sensing (QS). We are particularly interested in the Type 3 Secretion System (T3SS) and Type 6 Secretion Systems (T6SS) which deliver effector proteins directly into adjacent eukaryotic or bacterial cells and alter or halt gene expression and physiological processes in the targeted cells. T3SS and T6SS represent a major mechanism of interspecies interaction in P. aeruginosa, yet their regulation is not well understood. Building on our recent exciting findings, this proposed research aims to investigate the detailed regulations of T6SS and T3SS in P. aeruginosa, and to explore the T3SS-regulated, T6SS affecting Fem system and its role in interspecies interaction. The short-term objectives of the proposed research are to: 1) investigate the role of RtcB-mediated RNA modification in T6SS regulation, 2) verify the involvement of the ATP-dependent Clp protease in T6SS regulation, 3) elucidate the molecular basis underlying the connection of H3-T6SS with T3SS, pyocyanin production, protease activity and motility, and 4) characterize the regulon of the Fem system that potentially mediates interaction between P. aeruginosa and mycobacteria. Significance: The proposed research will reveal the molecular basis and new regulatory mechanisms of bacterial interspecies interactions. The role of RNA modification and ATP-dependent protease complex in the regulation of T3SS and T6SS will be characterized. Convergence of global regulatory pathways and the regulation of the potential interspecies signaling pathway Fem System will be uncovered. Such information will contribute to answering the fundamental question of how bacteria modulate their gene expression in response to other cells. Owing to the critical roles of these intercellular systems in pathogenicity and microbiota, the results will also lead to novel antibacterial targets and better management of both bacterial activities and microbial communities.