The T6SS toxins are powerful weapons for Pseudomonas' antibacterial strategy ‐ MRC

Abstract

Antibiotic resistance is on the rise and an antibiotics crisis looms. Efforts to find new sources of antibiotics and antimicrobials have redoubled. This includes exploring the potential of repurposing drugs currently used against non-infectious diseases and seeking to discover new antimicrobials in nature. Professor Alain Filloux, Imperial College London, is a world-leading expert in bacterial secretion systems who is investigating the type 6-secretion system (T6SS) of the multi-drug resistant bacterium P. aeruginosa. He is collaborating with Dr Laura Nolan in utilising a transposon mutagenesis technique â–“ transposon directed insertion-site sequencing (TraDIS) ‐ to search the P. aeruginosa genome for novel toxins secreted by the T6SS. Filloux and Nolan are conducting TraDIS both when the T6SS is active and when it is inactive, which will enable them to identify the related toxin. So far, the researchers have validated the use of TraDIS by identifying T6SS immunity genes, and corresponding toxins, that were already characterised as part of the T6SSâ–™ arsenal, confirming that a global and unbiased technique has the potential to identify novel toxins. By sequencing the mutant population, the team has also identified several potential novel toxin/immunity pairs, including Tse8/Tsi8, which targets the transamidosome involved in bacterial protein synthesis.