Bacterial Mucin Degradation in the Cystic Fibrosis Airways: A Potential Regulator of P. aeruginosa Pathogenicity.

Abstract

Cystic fibrosis (CF) is characterized by impaired mucociliary clearance, leading to mucus accumulation and chronic bacterial respiratory infections. Pseudomonas aeruginosa (PA) is a canonical pathogen in these infections and is found to nutritionally benefit from cross-feeding interactions with co-colonizing mucin-degrading bacterial genera. However, the impact of these cross-feeding interactions on the regulation of PA virulence remains unclear. Implementing a reductionist experimental approach, this thesis aims to investigate the proposed cross-feeding model to identify key exchanged metabolites and elucidate mechanisms underlying PA virulence. To successfully isolate and analyze variables of the multifaceted cross-feeding model, several specialized experimental tools and techniques were developed and described in Chapter 2. These tools were employed in Chapter 3 to fully characterize the growth profiles of several individual representative mucin-degrading bacterial species and investigate the effects of their secondary metabolites on PA physiology. Chapter 4 builds upon this by characterizing complex mucin-degrading bacterial communities enriched from clinical CF sputum samples, and again investigating their effects on PA physiology in vitro. These data establish validated methods for the field of CF research, expand our understanding of PA physiology, and pave the path for future development of novel targeted CF therapeutic strategies.