The influence of type VI secretion systems in antagonistic interactions between bacteria in the human nasopharynx

Type VI secretion systems (T6SS) have been extensively studied in bacteria inhabiting the gastrointestinal tract, where they can mediate antagonistic behaviour between pathogens. We have recently described a T6SS in Neisseria cinerea, a resident of the human upper respiratory tract (REF). The T6SS is encoded on a plasmid, and is active against Neisseria meningitidis and Neisseria gonorrhoeae, two human adapted pathogens, during growth in the laboratory. The range of killing exhibited by T6SS is determined by the toxic effector molecules delivered by the system, with some effectors able to modulate host cells and/or other bacteria. To date, we have identified six putative T6SS effectors, including predicted nucleases and a phospholipase.

 The aim of the project is to determine the role of the T6SS in i) bacterial antagonism when bacteria are in physiologically relevant environments, including while attaching to epithelial cell surfaces, and ii) modulating host cell responses to infection, with particular attention to epithelial and phagocytic cells. Finally, iii) the activity and contribution of individual effectors to bacteria:bacteria, and bacteria:host interactions will be determined by combining molecular genetics, biochemical and structural approaches.