Pseudomonas aeruginosa infections result in significant morbidity and mortality in people suffering from cystic fibrosis (CF). A key feature of these infections is that they involve biofilm communities. The expression of several key biofilm matrix components (e.g. the Pel,Psl exopolysaccharides and the matrix adhesin CdrA) are known to be initiated upon interaction with a surface. There are two known surface sensing systems in P. aeruginosa, Wsp and Pil- Chp, that both act by stimulating production of the intracellular signal c-di-GMP. The overall goals of this application are to investigate the Wsp surface sensing system, the signals it responds to, how it integrates surface sensing with the other surface sensing system Pil-Chp during the early stages of biofilm aggregate assembly. We will also examine the pathogenic fitness advantages of different surface sensing genotypes in murine models of infection and in vitro cellular immunological assays. This proposal will address gaps in our knowledge as to how surface sensing works and its contribution to pathogenesis. Future therapeutic strategies (particularly ones directed towards biofilm communities) will benefit from such knowledge.
This proposal is focused on examining the role of surface sensing in Pseudomonas aeruginosa biofilm formation and pathogenesis as it relates to chronic infection. The expression of several key biofilm matrix components are known to be initiated upon interaction with a surface. This proposal will address gaps in our knowledge as to how surface sensing works and its contribution to pathogenesis; future therapeutic strategies (particularly ones directed towards biofilm communities) will benefit from such knowledge.
Showing the most recent 10 out of 33 publications
