Regulation of Pseudomonas aeruginosa Chronic Infection Phenotypes

In Pseudomonas aeruginosa, the mucoid phenotype due to the overproduction of the polysaccharide alginate has been associated with chronic lung infections and clinical decline in cystic fibrosis (CF) patients. P. aeruginosa strains are monitored along with the host response in a murine model of chronic respiratory colonization to determine the genetic mechanism controlling phenotypes associated with emergence of mucoid strains. The long-term goal of these studies is to identify bacterial factors that can be targeted to inhibit chronic lung infections and host factors that can increase bacterial clearance and therefore improve the lives of CF patients.


Developing laboratory models that accurately reflect P. aeruginosa infection dynamics in chronic infections

Laboratory models of human infections are essential for studying pathogen behavior and physiology during infection, but it is often not known how well pathogen physiology in a model accurately reflects what is happening in a human. Our research focuses on chronic lung infection in people with the cystic fibrosis (CF). CF is a genetic disease which results in mucus (sputum) buildup in the lung airways, creating a hospitable environment for pathogens like Pseudomonas aeruginosa. Using different CF infection models, transcriptomics, and a quantitative framework that we use to evaluate model accuracy, we are working to develop a mouse model where P. aeruginosa physiology more accurately reflects what happens in a CF lung than the standard mouse model. A better mouse model will make important contributions to preclinical work that will ultimately be used to inform development of novel treatments for lung infections in people with CF.

Right Figure: Accuracy of CF infection models. Accuracy scores of genome-wide P. aeruginosa gene expression in synthetic CF sputum medium (SCFM2), in PBS (standard input), a mouse model that was inoculated with P. aeruginosa grown in SCFM2 (SCFM2-infected mouse) and a mouse model that was inoculated with P. aeruginosa suspended in PBS (Standard-infected mouse). The accuracy score (AS2) of each sample represents the percentage of P. aeruginosa genes are expressed at a level within two standard deviations from the level at which those genes are expressed P. aeruginosa found in CF sputum.