The lungs of people with CF become chronically infected by a variety of organisms. Among these, Pseudomonas aeruginosa, a gram-negative environmental bacterium, becomes more common with patient age, and detection of this microbe is associated with worse lung disease. P. aeruginosa undergoes genetic changes as it adapts to the CF airway environment, and some of these changes (and the altered bacterial behaviors they often confer) have been associated with persistent infection and even worse lung disease. Therefore, studying these adaptive changes could identify better treatments to prevent infection and lung disease progression. However, little is known about how these changes occur over time, and how these adaptive changes relate to progression of disease, persistence of infection, or response to treatment.
We are currently studying the changes that occurred in P. aeruginosa isolates collected from a large number of children over many years, beginning with new detection in each case. The figure below shows our results for about 22 different bacterial behaviors. In some cases, analyzing these behaviors may be able to predict stage of infection. These behaviors may serve as useful biomarkers of advanced disease or persistent infection, and may identify patients who are candidates for specific treatments. These ideas will be the topics for planned clinical studies.
Figure Legend: Analysis of 22 different bacterial behaviors among ~2600 isolates of P. aeruginosa collected from children with CF and newly-detected, intermittent, and chronic infection stages. (a) Each horizontal line represents cultures positive for P. aeruginosa from a different, individual patient, and each dot is color-coded as indicated to categorize the stage of infection at that culture. (b) Proportion of cultures of each type (stage) that had P. aeruginosa isolates exhibiting the indicated bacterial behavior. Changes in the production of the P. aeruginosa factors pyoverdine and protease, and bacterial motility, best distinguished infection stage.