Effect of Exopolysaccharides on Pseudomonas aeruginosa Physiology

Abstract

Bacteria form multicellular aggregates called biofilms. Cells in biofilms are encased by aself-produced matrix composed of proteins, exopolysaccharides (EPS), nucleic acids, and lipids. Biofilm matrix composition mediates how bacteria interact with one another and their environments. The biofilm matrix of the opportunistic pathogen P. aeruginosa contains up to three chemically distinct EPS: Pel, Psl, and alginate. EPS production is necessary for robust P. aeruginosa biofilms formation, however, the amount and number of EPS produced varies between strains and growth conditions. Differences in EPS production alter how P. aeruginosa interacts with its environment, from promoting initial attachment to enhancing antimicrobial tolerance. The goal of my doctoral thesis work has been to determine whether the EPS Pel and Psl are produced and relevant during infection, and to understand how their production is regulated. In this dissertation, I provide evidence that Pel and Psl are produced and co-localize with P. aeruginosa in cystic fibrosis (CF) lung infections. I also demonstrate that ionic interactions between Pel and extracellular DNA (eDNA) increase tolerance to aminoglycoside treatment. Additionally, I determine that cell-association of Psl is promoted post-translationally by the diguanylate cyclase SiaD, which stimulates initial attachment to surfaces. This work provides valuable insight into how and when P. aeruginosa EPS are produced. These and future studies will inform practices to prevent patient colonization and improve the efficacy of treatments.