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Title: Novel inhibitors of adhesin-receptor interactions involved in microbial infection at mucosal surfaces
Author: O'Mahony, Rachel Mary
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2006
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Microorganisms are becoming increasingly resistant to current antimicrobial agents and therefore new strategies and agents are being developed to combat infection. One strategy is to target and block the first step of microbial infection (adhesion of the microbe to the host tissue) by using molecules that mimic (or antibodies against) the microbial adhesin or its complementary host cell receptor. Plants have also been shown to provide natural sources of antimicrobial substances as well as inhibit microbial adhesion. One major problem in adhesion-inhibition studies has been the accurate quantification of adhesion. Most investigators have relied on manual counting while a few have used automated methods using image analysis software. The first aim of this study was therefore to compare the effectiveness of several current software packages, to develop the most accurate method of quantification and to use this method to test potential inhibitors of microbial adhesion. The organisms under investigation in this project were Candida albicans and Helicobacter pylori, both of which are becoming resistant to available antibiotic treatments. A new and accurate method of quantification was developed for assessing microbial adhesion using 'Metamorph' image analysis software. Aided by this system, several domain antibodies, carbohydrates and plant extracts were found to be successful inhibitors of C. albicans and H.pylori adhesion in vitro and therefore have the potential to form the basis of new and alternative therapies to treat infection caused by these microorganisms. Additionally, because it is not fully known why H. pylori preferentially colonises specific topographical regions of the human stomach, the second aim was to compare its adhesion to different topographical regions of the stomach, in an attempt to explain this phenomenon. No difference was found between the receptors present in the antrum or fundus of inflamed human stomachs. However, further investigations involving both inflamed and non-inflamed stomachs are warranted.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available