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Title: The role of membrane lipid remodelling in the antimicrobial resistance arsenal of Pseudomonas aeruginosa
Author: Jones, Rebekah A.
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2020
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Pseudomonas aeruginosa is a common cause of hospital-acquired infections, with prevalence in immunocompromised individuals and multi-drug resistance capabilities. Phosphate stress triggers a cascade of virulence factors in P. aeruginosa, with phosphorus scarcity known to occur in several infection models. Here I show that P. aeruginosa is able to modify its membrane lipid composition in adaptation to low phosphorus availability, termed lipid remodelling, in a process that substitutes membrane phospholipids for non-phosphate lipid classes. High performance liquid chromatography coupled to mass spectrometry (HPLC/MS) confirmed the production of glycolipids in response to phosphate stress in P. aeruginosa. An intracellular phospholipase C, PlcP (PA3219), removes phospholipid head groups, liberating diacylglycerol to become the base for glycolipid synthesis. Heterologous expression in Escherichia coli confirmed two glycosyltransferases, PA3218 (Agt1) and PA0842 (Agt2), catalyse the production of monoglycosyl diacylglycerol (MGDG) and glucuronic acid diacylglycerol (GADG) glycolipids, respectively. When grown under low phosphate conditions, P. aeruginosa has significantly decreased sensitivity to antimicrobial peptide polymyxin B, compared to growth with sufficient phosphate. Here, I show that mutants defective for glycolipid synthesis are less able to survive when challenged with polymyxin B under low phosphate conditions, compared to wild type. Proteomic analyses also revealed potential changes in carbapenem sensitivity and virulence factor expression as a result of lipid remodelling. Critically, this study emphasises a role for glycolipids beyond simple phosphate conservation, in proposing antimicrobial resistance trade-offs as a result of this phenotypic adaptation to phosphorus stress in P. aeruginosa.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QP Physiology ; QR Microbiology