2C OR NOT 2C? THE ROLE OF SHORT CHAIN FATTY ACID CATABOLISM IN PSEUDOMONAS AERUGINOSA VIRULENCE AND PATHOGENICITY

The WHO recently announced that Pseudomonas aeruginosa is a top-level "critical priority threat" to human health, and that new antimicrobial strategies are urgently required to combat the infections caused by this organism. P. aeruginosa exhibits a remarkable predilection for infecting immunocompromised individuals, and when it comes to food, it is a genuine connoisseur of fatty acids. However, it turns out that by blocking certain short chain fatty acid (SCFA) catabolic pathways, P. aeruginosa can be stopped in its tracks. This is because an inability to catabolise these compounds delivers a powerful "double whammy" to the organism, leading to both metabolic insufficiency and diminished virulence, allowing the host enough time to clear the infection before it establishes itself. In this lecture, I will explore how, with a better knowledge of Pseudomonas SCFA catabolism, we can develop small molecules to combat P. aeruginosa pathogenicity (and also learn a good deal of new biology along the way). Serendipity and some excellent colleagues with collaborative spirit have been our friends, and in the course of the talk we`ll take a tour encompassing how the organism causes disease, its love for fatty acids, what happens when it can`t eat these, and how atomic resolution structures and sheer good luck have aided our drug design efforts. Pseudomonas does things differently compared with most other bugs, and if there is a take-home message to be had, it is that we cannot always extrapolate from our knowledge of E. coli to figure out how other bacteria work.