You are what you eat: dietary peccadillos of a pathogen

Host: Dr Megan Bergkessel 

Venue: Sir Kenneth & Lady Noreen Murray Seminar Room CTIR 2.84

Abstract  

In this talk, I discuss the dietary preferences of an opportunistic human pathogen, Pseudomonas aeruginosa. This organism exhibits an exquisite predilection for colonizing soft tissues in the body, although it seems to have a particular soft spot for the airways, especially among individuals (such as those with cystic fibrosis (CF)) who are predisposed towards infection. Quite why it likes the airways so much is still not entirely clear, although a major contributory factor is the abundance of fatty acid derivatives at that site - and P. aeruginosa loves fatty acids. Unlike E. coli - which has more of a sweet tooth, and generally eschews fatty acids in favour of carbohydrates - Pseudomonas aeruginosa encodes no fewer than six pathways of beta-oxidation. However, these pathways all converge at a common "pinchpoint" (the fatty acyl-CoA dehydrogenase-catalyzed reaction); here, we identify the acyl-CoA dehydrogenases that do the job (and there are >20 homologues encoded by P. aeruginosa to choose from there), and show how judicious swapping of residues in the selectivity filter of the enzymes can radically change their substrate specificities. We also show that the organism is geared up to maximize use of the acetyl-CoA thus generated, becoming critically dependent on proper functioning of the glyoxylate shunt in infection scenarios. These are not esoteric observations either: they are important because P. aeruginosa uses "nutritional cues" to regulate the expression of clinically-relevant phenotypes such as virulence and AMR, and this too will be discussed.