Many pathogenic bacteria that cause life-threatening human diseases like the bubonic plague, pneumonia, and food poisoning, inject toxins into the host to establish infection. Gram-negative bacteria inject toxins using a syringe-like nano-machine known as the Type III Secretion System. The toxins gain access to the target cell through a channel (the type III translocon) on the target cell membrane, formed by two secreted bacterial proteins termed translocators. Formation of this translocon is critical for bacterial infection, and blocking the translocon assembly would interfere with the infection. Therefore, understanding how translocators interact to assemble functional channels is essential for the development of novel therapeutic agents to combat these pathogens.
In the work published this week in the Journal of Biological Chemistry, the Heuck lab unveiled new insights on the interaction and assembly mechanisms of the Pseudomonas aeruginosa channel-forming proteins PopB and PopD. Researchers Y. Tang, F. Romano, and M. Brena, led by Prof. Heuck showed that PopB and PopD formed hetero-dimers on lipid membranes, suggesting that an early PopB and PopD interaction is essential for guiding the assembly of the channel. Moreover, they showed that the interaction of PopB with PopD is required to properly insert PopD into the target cell membrane and assemble functional channels.