Bacteria employ diverse toxins as molecular weapons used to inhibit growth of bacterial competitors or to
infect eukaryotes. Many toxin genes remain hidden in bacterial genomes and their elucidation can lead to
an improved understanding of microbial ecology Furthermore, these toxins can promote development of many
applications such as diagnosis and treatment of infectious diseases, vaccine development, biological control of
plant diseases, and development of new cell biology tools based on the cellular targets of these toxins.
We study two functionally-related bacterial secretion systems that are used to translocate toxins into
neighboring cells: The Type VI Secretion System (T6SS) and the Extracellular Contractile Injection System (eCIS).
These toxin delivery systems are important for microbial interaction with various organisms in diverse ecosystems,
and they can be re-programmed to function against pests and pathogens.
T6SS is a nano-weapon employed by ~25% of Gram-negative bacteria to inhibit either competing bacteria or eukaryotic cells. A membrane-bound ‘launching device’ protein complex contracts and fires a tube with a sharp tip into the target cell or the extracellular medium. Toxic effector proteins are translocated through the tube or are bound to the spike and are released inside the target cell where they exert their toxicity. These toxins degrade cellular components such as the cell wall, cell membrane or nucleic acids. We develop computational methods to predict T6SS effectors in large set of bacterial genomes, and experimentally validate our predictions in the lab.
The bacterial and archaeal eCIS system is encoded in thousands of genomes. It is a compact cell-free version of the T6SS that resembles a contractile phage tail (a headless phage). eCIS particles are likely released to the medium when the eCIS-encoding bacterial cell is lysed. The particle attaches to and translocate toxins into the target cell. Unlike the extensively studied T6SS, very little is known about eCIS. The few experimentally studied eCISs mostly interact with invertebrates and confer insecticidal activity or induction of host development. We are interested in elucidating the biological function and regulation of the mysterious eCIS in different microbes, with a focus on eCIS of plant-associated bacteria.
In recent years there is a growing interest in the plant microbiome as a means to gain a more efficient and sustainable agriculture by increasing plant productivity, protecting against plant diseases, and reducing usage of fertilizers and pesticides. We now have good understanding of plant microbiome composition (“who is there?”) but a comprehensive understanding of the plant microbiome gene function lags far behind. The microbiome genes constitute a 'second genome' to the plant that confer various features, including biotic stress (plant diseases), nutrient provision, plant hormone modulation that affect plant defense and plant growth, and direct pathogen control. The molecular mechanisms underlying plant-microbe interactions are poorly understood and are crucial so we can harness the plant microbiome to increase crop yields. We study the function of plant-associated bacterial genes by combining computational and molecular microbiology and plant biology.