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Download StatisticsSheehan, Emma (2020). The role of antibody in the killing of Pseudomonas aeruginosa by human sera. University of Birmingham. Ph.D.
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Sheehan2020PhD.pdf
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Abstract
Antibody plays an important role in the protection against many different infections. Here the role of antibody in the protection against P aeruginosa infection was further investigated. Patients suffering from chronic lung infection with P. aeruginosa can produce antibodies that protect the bacterium from the bactericidal activity of serum. The effect of the removal of these antibodies on the P. aeruginosa population was investigated. One clonal lineage appeared to be eradicated from a patient with a multi-lineage infection. However, the treatment did not promote strain replacement in either patient suggesting that a single strain was able to persist within a specific niche in the lung. The role of antibody in the protection against P. aeruginosa infection by sera from healthy individuals was further investigated. Killing of P. aeruginosa was complement-dependent and in some instances, complement alone was sufficient to elicit killing. P. aeruginosa-specific antibodies enhanced the killing of some strains and blocked the killing of others. Inhibitory antibody was identified in healthy serum, suggesting that healthy individuals can produce inhibitory antibodies without an active infection. The mechanism of inhibitory antibodies is not fully understood. A transposon library was constructed in a strain of P. aeruginosa isolated from a non-cystic fibrosis bronchiectasis patient and used to define the essential genome. This was the first library to be constructed in a multi-drug resistant respiratory isolate and consisted of 577,494 unique mutants. The library can be used as a tool to provide further insight into the mechanism of inhibitory antibodies and has the potential to lead to the development of new treatments and diagnostics for patients with inhibitory antibody.
| Type of Work: | Thesis (Doctorates > Ph.D.) | |||||||||
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| Award Type: | Doctorates > Ph.D. | |||||||||
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| Licence: | All rights reserved | |||||||||
| College/Faculty: | Colleges (2008 onwards) > College of Medical & Dental Sciences | |||||||||
| School or Department: | Institute of Microbiology and Infection | |||||||||
| Funders: | Biotechnology and Biological Sciences Research Council | |||||||||
| Subjects: | Q Science > QR Microbiology Q Science > QR Microbiology > QR180 Immunology R Medicine > R Medicine (General) |
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| URI: | http://etheses.bham.ac.uk/id/eprint/10531 |
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