A mucosal surface model of pseudomonas aeruginosa infections
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2012
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Abstract
In the human body, mucosal sites such as the lungs, eyes, gastrointestinal tract and urinary tract are often the target of bacterial infections. One of the most notorious bacterial species known to infect mucosal surfaces is the opportunistic pathogen Pseudomonas aeruginosa. As such, there has been much research devoted to studying the mechanisms by which P. aeruginosa infects these surfaces, particularly how it causes chronic infections as these infections are problematic and difficult to eradicate. However, because P. aeruginosa is an opportunistic pathogen - in that it typically causes infection of mucosa! sites when they are compromised by disease, injury, or implanted medical devices - it has proved difficult to model infections by these bacteria. Consequently, in this work, we hypothesized that we could develop a novel model using the rat prostate for studying acute and chronic P. aeruginosa infections at mucosal surfaces. Unlike current mammalian models of chronic infections, this model has an advantage: chronic infections can easily form at the prostate mucosal surface without foreign body assistance. Therefore, using this model, we were able to study how chronic P. aeruginosa infections were influenced by processes that occur within the biofilm - a mode of adherent bacterial growth that is resistant to clearance. We found that signalling via quorum sensing was required to maintain a chronic infection, but this was likely due to its role in biofilm function rather than formation. We also showed, for the first time, that generation of variants associated with biofilm growth occurred in vivo using similar genetic pathways previously identified in vitro. Furthermore, we ascertained that the generation of variants could be critical for maintaining an infection, and that a heterogeneous population of variants was produced during mucosal surface infections. Finally, we expanded on the utility of our model and showed that diversity via multi-isolate infections affected chronic P. aeruginosa virulence. Thus, altogether, using our novel prostate model we were able to determine that signalling and diversity generation were important for chronic P. aeruginosa infections at mucosa! surfaces. These findings should have important implications for the development of better therapeutics against P. aeruginosa.
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Bibliography: p. 214-233
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Nelson, L. K. (2012). A mucosal surface model of pseudomonas aeruginosa infections (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/4614