Chronic infection and inflammation at mucosal surfaces

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A thin layer of mucous separates the luminal surface of the respiratory, digestive, and urogenital tracts from the outside world, making these surfaces of the body the most prone to infection and inflammation. My laboratory, using the rat prostate as a model system, has studied the role of bacterial virulence factors, which are weapons used by bacteria to attack the host, in helping bacteria to establishing chronic infections by forming biofilms at these surfaces. Biofilms are bacteria growing as interactive colonies within a slime layer attached to tissues or implanted medical devices that are less susceptible to the host immune system and to antibiotic treatment, thus allowing them to persist. We have developed new technologies for assaying antimicrobial susceptibility of biofilms, which has resulted in a multifactorial model to explain the resistance of biofilms. In future, we will continue to study infection and inflammation at mucosal surfaces and mechanisms of antimicrobial resistance of biofilms. First we will expand the use of the prostate as a more general model of mucosal inflammation to study Pseudomonas biofilm infections as seen in cystic fibrosis (CF). Since the normal lung clears Pseudomonas infections readily we will use the prostate, a mucosal surface more susceptible to biofilm formation, as a model of these infections of the CF lung. We will also move the model into the mouse, which has become the prime model to study the immune response. This will allow us to better ascertain the contribution of the host's immune system to the inflammatory disease process initiated by biofilm formation. Secondly, we will continue our study of the adaptations of bacteria in biofilms that result in their reduced antimicrobial susceptibility by characterizing the proteins made by biofilms under challenge in order to define the mechanisms initiated to stave off elimination by antibiotics. Further we will look at the role of enzymes involved in limiting damage from reactive oxygen species in contributing to the stability of biofilms under antimicrobial stress. We anticipate that these studies will allow us to better understand and in the long term control chronic mucosal infections.