Birdwatching as a microbiologist: What bacterial populations of Pseudomonas aeruginosa tell us about the type VI secretion system, host-microbe interactions and bioengineering

Bacteria use sophisticated molecular machineries to interact with other cells and take up nutrients. One such machinery is the type VI secretion system (T6SS) that is found in a variety of bacteria including the opportunistic pathogen Pseudomonas aeruginosa. Despite a remarkable understanding of the T6SS structure and molecular biology in P. aeruginosa reference strains, less is known about its biodiversity and role during disease. We use a broad range of approaches to better understand how and why P. aeruginosa bacteria use their T6SS.

To study the biodiversity of the effector proteins that are secreted with the T6SS (and include some proteins wit lipase activity), we performed molecular population genetics on roughly 2000 P. aeruginosa strains. Whereas some effector genes were found in the genomes of nearly every strain, others were not. According to the pangenome concept, we refer to them as core effectors and accessory effectors, respectively. Based on the characteristics of the effector proteins that are encoded in genes of each category, we identified generalizable principles that might aid in the engineering of proteins for delivery by the T6SS or other contractile injection devices.

To gain a better understanding of T6SS-mediated host-microbe interactions in a bacterial infection, we used the insect Galleria mellonella as a model system and identified effectors with previously unknown anti-eukaryotic activity that contribute to the virulence of P. aeruginosa. Further, we identified phases during infection in which the T6SS is advantageous or disadvantageous for the infecting bacterium. To specifically study the host’s immune response to the T6SS, we recruited a cohort of over 100 patients colonized with P. aeruginosa and identified a subgroup of patients with an elevated anti-T6SS immune response.