Bacteria use various mechanisms to secrete proteins that will shape their environment. The type VI secretion system (T6SS) is one of the most recently discovered bacterial protein secretion systems. It is widespread in Gram-negative bacteria. The T6SS is macro-molecular machine that can deliver proteins, called effectors, to the environment or directly into adjacent recipient cells, either bacterial or eukaryotic, mediatimg antibacterial activities or virulence activities, respectively.
Developing novel antibacterial treatments
We use synthetic biology techniques to engineer a T6SS-based platform that will be used as a 'plug-and-play' antibacterial treatment. We are also identifying potential targets that will be used to develop new antibacterial drugs. These treatments will cause pathogens to kill their their kin for us.
Salomon and Orth, Current Biology, 2015
Identifying Novel toxins and mechanisms of action
T6SSs can deliver effectors that mediate antibacterial activities, or that manipulate eukaryotic cellular processes to the advantage of the pathogen. We are developing methodologies to identify novel T6SS effector classes and families. Using biochemical, proteomic, genetic, and bioinformatic approaches, we study the functions and targets of these new effectors.
Through proteomic and bioinformatic analyses, we identified a widespread class of polymorphic T6SS effectors named MIX-effectors. These effectors share an N-terminal domain named MIX (Marker for type sIX effectors), and often neighbor transposable elements that allow them to be shared between bacterial species and enhance bacterial fitness. MIX-effectors carry various toxin domains at their C-termini, including lipases, pore-forming toxins, nucleases, de-amidases, and many toxin domains of unknown function and targets. We study the mechanism of secretion of these MIX-effectors, investigate the role of the MIX domain in T6SS-mediate secretion, and identify toxic activities and targets of these effectors.
Dar et al, Marine Drugs, 2018
T6SSs are tightly regulated machines, and in many cases are only activated upon sensing specific cues in the environment. Our previous studies revealed that the emerging pathogen Vibrio parahaemolyticus, a major cause of food-borne gastroenteritis world-wide, harbors two T6SSs that are differentially regulated by cell density, salinity, and surface-sensing. At least one of these systems, T6SS1, mediates inter- and intra-species bacterial killing using a suite of effectors delivered into adjacent competing bacteria. Using a fluorescence-based bacterial competition assay that we recently developed, we are identifying key regulatory components of the T6SS.