The Bacterial Assassin and its Tool Kit

Midway through our journey through the microbial world, Dr. Maria Hadjifrangiskou joined the class on February 3rd, 2023, to narrate a portion of our tour “Warzone Travel: Bacterial Fight Club.” In this session Dr. Hadjifrangiskou discussed the amazing ability of some bacteria to shoot protein daggers into other cells as a form of attack or defense. This incredible structure is called the type VI secretion system (T6SS).

            The T6SS is a highly dynamic nanomachine expressed in Gram negative bacteria, like Vibrio cholera and Pseudomonas aeruginosa. It consists of several proteins that assemble to form a rod-like structure within the bacterium, which is topped with a spike shaped protein called VgrG and subsequently propelled out of the cell by a buildup of intracellular pressure [1]. This structure also contains poisonous cargo that is transferred to the neighboring cell when punctured. These “poison darts” can kill the target cell by preventing cell division, disrupting the lipid bilayer, compromising protein production, and more. Contact between bacteria is often necessary for an effective attack with the T6SS, as the protein cannot be shot with enough force to cross larger distances. In addition, this contact is even used as an indicator to start an attack against an enemy bacterium that might slip past the defenses.

            While the T6SS is an important tool for bacterial assassins, some are better trained than others and you might even say some have a strong sense of justice. V. cholera is a Gram-negative bacteria known to cause cholera in humans, but its use of the T6SS is not highly regulated [2]. The V. cholerae that express the T6SS abuse the power of the system, attacking at random and with voracity. Another Gram-negative bacterium, P. aeruginosa, is highly specific in its targets, raising a counterattack only when directly threatened [3]. Studies from the Mekalanos lab characterized the differences in how these two bacterial species use the T6SS to their advantage. When comparing P. aeruginosa attacks to V. cholera attacks, they observed that P. aeruginosa only attacked V. cholera when it was actively deploying its T6SS. P. aeruginosa did not attack V. cholera with non-functional T6SS, instead living peacefully in the heterogeneous mixture [3]. These interactions could be highly important for mediating communication between different types of bacteria in communities.

             Despite the somewhat unsettling idea of bacteria having assassin-like tools, the T6SS is an extremely interesting area of investigation. It appears to be important not only in competition, but also in communication and maintenance of biofilms. Most organisms within a given community have genes that encode the T6SS, yet only 10-12% express the system, raising the question of how it is decided which bacteria will rise to the front lines and fight for their territory. There are still many questions to be explored in this field to learn more about how bacteria can fight each other, other species of bacteria, and even host cells.

References

  1. Coulthurst, S. (2019). The Type VI secretion system: a versatile bacterial weapon. Microbiology165(5), 503-515.
  2. Crisan, C. V., & Hammer, B. K. (2020). The Vibrio cholerae type VI secretion system: toxins, regulators and consequences. Environmental Microbiology22(10), 4112-4122.
  3. Basler, M., Ho, B.T., and Mekalanos, J.J. (2013) Tit-for-tat: type VI secretion system counterattack during bacterial cell-cell interactions. Cell 152: 884–894.