Evolution of P. Aeruginosa Biofilm Hyper-Production in Light of Local Fluid Viscosity and Multispecies Interactions within the CF Lung

Project Leader

Carey Nadell, Ph.D.
Assistant Professor of Microbial Ecology
Department of Biological Sciences
Dartmouth College

Pseudomonas aeruginosa is often the most densely populated and damaging of opportunistic pathogens that colonize the lungs of patients with Cystic Fibrosis (CF). However, other bacteria (e.g. Staphylococcus spp., Burkholderia spp., Klebsiella spp.) and fungi (e.g. Candida spp., Aspergillus spp.) are typically present as well, causing polymicrobial infections. P. aeruginosa evolves into diverse sub-populations during chronic infections, and there are similarities in the evolutionary trajectories of these populations between patients. For example, CF isolates of P. aeruginosa often exhibit hyper-secretion of Alginate, Pel, or Psl, which are secreted polysaccharide components of the extracellular matrix that binds bacteria together into multicellular biofilms. Biofilms are more efficient in exploiting local resources and far more tolerant to antibiotic treatment than solitary cells on their own.

The causal factors underlying consistent evolution of matrix hyper-secretion by P. aeruginosa in the CF lung environment are not known. The biofilm matrix can block the diffusion of some solutes, including antibiotics that are administered to CF patients, and the matrix can confer resistance to shear stress imposed by fluid flow. On the other hand, matrix hyper-secretion is also known to confer selective advantages during within-species competition: prior work has shown consistently across Pseudomonas spp. and Vibrio spp. that matrix hyper-secreting strains outcompete their parental strains on glass in simple microfluidic environments. Whether this is true for polymicrobial interactions remains unknown, nor is it clear how the fluid viscosity of the CF lung affects biofilm matrix evolution. In this project, we will investigate these open questions using approaches from microfluidics, confocal microscopy, bacterial genetics, and microbial ecology.