Principal Investigator: Pradeep Singh, M.D.
Consensus has emerged that cystic fibrosis (CF) airway infections are caused by P. aeruginosa living in biofilms. Biofilms are communities of bacteria encased in a polymeric matrix. Thus, improving clinical outcomes may require interventions that can eradicate or prevent biofilm formation. Unlike the P. aeruginosa biofilms generated by laboratory reactors, CF biofilms consist of cell clusters (often termed microcolonies) that grow within the sputum gel. We hypothesize that the genetic factors required for biofilm formation within a gel are different from those required on the inanimate surfaces found in laboratory reactors. To test this, we developed a model in which biofilms grow in sputum gels, and found that wild type P. aeruginosa forms cell clusters in gels that resemble CF biofilms in term of morphology and tobramycin resistance. Here we will determine whether gel biofilm formation produces generalized resistance to antibiotics and biocides, and whether CF isolates that are deficient in biofilm formation in reactors form biofilms in the gels. We will also investigate whether CF sputum promotes biofilm formation by using it as the sole nutrient source in the gel model. Finally, we will determine whether the bacterial functions that mediate biofilm formation in lab reactors also effect biofilm formation in sputum gels. These experiments could advance our understanding of biofilm growth in CF and may provide novel targets for anti-pseudomonal therapies.