The Type VI Secretion System (T6SS) is a molecular machinery of Gram-negative bacteria which facilitates pathogenesis and interbacterial competition. Understanding the dynamics and function of T6SS is essential for therapeutic insights. Burkholderia is a Gram-negative bacterial genus with species such as B. pseudomallei and B. cenocepacia, which are the causative agents of high mortality diseases such as Melioidosis and Cystic Fibrosis-associated pneumonia in humans. Burkholderia contain one to six different T6SS. One of the systems, T6SS-5, can cause mammalian cells to form multinucleated giant cells (MNGC). These play an important role in virulence because they allow intracellular spread of bacteria. Moreover, Burkholderia uses T6SS-1 to outcompete other bacteria to persist in the host and the environment.
In this project, molecular cloning, mammalian cell infection assays and bacterial competition assays, combined with confocal imaging and transcriptomic analysis, will be carried out to determine the dynamics and regulation of T6SS in phagocytic and non-phagocytic mammalian cells and during bacterial competitions. Furthermore, the role of host cell signals in T6SS regulation will be explored. This will provide insight on therapeutic targets for inhibiting the spread and attenuating virulence of Burkholderia infections.