A Type VII-secreted toxin enables inter-mycobacterial competition

Most bacteria have evolved mechanisms to compete with other bacteria, often through the specialised secretion of proteinaceous toxins. However, mycobacteria have not previously been reported to engage in this form of competition. The thick and unusual mycobacterial cell wall, comprised of peptidoglycan, arabinogalactan and mycolic acids, is generally thought to be highly protective to these bacteria. Here, we show that some mycobacteria can use endo-D-arabinanases of the GH183 family for inter-bacterial competition. These microorganisms secrete an endo-D-arabinanase effector via the type VII secretion system (T7SS) that cleaves the arabinogalactan layer of the mycobacterial cell envelope. We describe the molecular basis for this activity using structural biology and biochemistry, and identify a protein family that protects the bacterium from the activity of this toxin. The widespread presence of genes potentially encoding similar T7SS-secreted toxins in the Mycobacteriales suggests extensive inter-mycobacterial competition.