Structure and function of the type VI secretion system in bacterial pathogens

We will employ a plethora of structural, biochemical and genetics tools and a panel of T6SS effector mutants of V. cholerae and P. aeruginosa, two T6SS model species. We have three specific aims:

• How are effectors loaded in situ and involved in T6SS assembly?
• What are the exact functions of the T6SS membrane-baseplate complex (MBC) components?
• Are effector-cognate chaperones localized together with effectors within the MBC?

The details

Microbial pathogenesis poses a serious threat to public health. Of the diverse virulence mechanisms found in gram-negative pathogens, the type VI secretion system (T6SS) is unique for its dual role in killing bacterial competitors and eukaryotic cells by injecting toxins directly from a donor cell to a recipient cell. Therefore, the T6SS plays a key role in microbiome composition and functions.

Evolved from contractile bacteriophage tails,  the  T6SS is featured with a long (~1 um) double tubular sheath- tube structure that is connected to a transmembrane complex and a baseplate structure. Assembly of the sheath-tube initiates from the baseplate and extends to the other side of the cell, involving at least 13 conserved structural proteins. How these multi-protein complexes are coordinated spatially and temporally remains elusive.

In this joint project, we plan to combine the strength of structural biology at UoM and bacterial genetics at SJTU to tackle the assembly process using several important model pathogens and a panel of genetic mutants.

The project will be complemented by the project on 'Investigating the molecular mechanism of effector secretion by the bacterial type IV secretion system' and the collaboration will ensure the successful completion of both projects.

The graduate researcher on this project is: Shubha Venkatesh Airbail Udupa

Supervision team

Shanghai Jiao Tong University supervisor:
Professor Tao Dong

University of Melbourne supervisors:
Dr Debnath Ghosal