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Investigating the effects of large genomic deletions on Beta lactam resistance in Pseudomonas aeruginosa.
Graduate Thesis/Dissertation   Open access

Investigating the effects of large genomic deletions on Beta lactam resistance in Pseudomonas aeruginosa.

Georgina Trulee Mashlan
Master of Science - MSc, University of Otago
University of Otago
2022
Handle:
https://hdl.handle.net/10523/14120

Abstract

Pseudomonas aeruginosa Genome deletions Beta-lactam resistance resistance antibiotic galU meropenem ceftazidime
Pseudomonas aeruginosa is a leading cause of hospital acquired infections worldwide and chronically infects people with Cystic fibrosis (CF). Large genomic deletions (over 200 kb) appear in response to selection with increasing concentrations of meropenem. These large deletions increase resistance to meropenem and ceftazidime by up to 4 fold. The changes in MIC are due to a single gene deletion of galU. Large deletions contain numerous other genes however. The impacts of the loss of these genes include changes to expression of biofilm and flagellar components, amino acid degradation, and metabolism genes as revealed by RNA-seq analysis. As large deletions have emerged as a novel resistance mechanism easy identification will be important in the understanding of the role and mechanism of resistance conferred by deletions. Therefore a novel deletion characterisation pipeline was proposed in order to identify and characterise large deletions in a high throughput manner. This pipeline was able to characterise known deletions as well as propose novel deletions in a clinical isolate data-set.
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