Liquid crystal Pseudomonas aeruginosa biofilms

Fellow: Patrick Secor, PhD
Pulmonary and Critical Care

Mentor:  Pradeep Singh, MD
Professor, Microbiology and Pulmonary and Critical Care

Pseudomonas aeruginosa is a major pathogen in Cystic Fibrosis (CF) and the capacity of P. aeruginosa to produce biofilms is key to its virulence. Although the production of filamentous bacteriophage by P. aeruginosa biofilms is well known, the functional consequence for their presence is not. The goal of the research proposed here is to understand how filamentous phage act as structural components of the biofilm matrix and thus contribute to pathogenesis in the CF lung.

The central hypothesis of this proposal is that phage produced by P. aeruginosa in the CF lung contributes to the structural integrity and overall organization of the biofilm matrix by organizing liquid crystal-like structures out of available polymeric materials. These organized polymeric structures likely impact important biofilm phenotypes such as adhesion and antibiotic tolerance. I will pursue these studies in three Specific Aims:

1. Determine if phage organize polymers into a crystalline network in P. aeruginosa biofilms.
2. Define the contribution of phage to antibiotic tolerance and bacterial adherence.
3. Determine if disrupting phage-organized biofilms impacts antibiotic tolerance and adherence.

Insight into how phage contribute to P. aeruginosa biofilm formation may lead to novel therapeutic strategies to specifically target and hinder the ability of bacteria to establish communities within CF lungs. Such strategies may enhance the antibiotic susceptibility of P. aeruginosa, a concept supported by my preliminary data. Furthermore, support from a CFF-RDP Fellowship would greatly aid in development of this project for future, career development funding, such as a K99/R00 application.