Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.641350
Title: Putative virulence factors and novel antimicrobial targets of the Burkholderia cepacia complex
Author: Bartholdson, Sara Josefin
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2009
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Abstract:
Members of the Bcc, previously described as non-mucoid, produced copious amounts of EPS when onion extract was provided as a sole nutrient. When investigating the onion extract content, it was found that fructose, sucrose and alcohol sugars were able to induce this change in phenotype. Interestingly, none of the virulent B. cenocepacia ET-12 isolates was able to produce EPS on any medium tested. This loss of EPS phenotype correlated with an 11 bp deletion in bceB, which is part of the bce gene cluster associated with the biosynthesis of cepacian, a previously characterised Burkholderia EPS. It has been proposed that instead of a non-mucoid to mucoid conversion, which is strikingly characteristic of P. aeruginosa infections in CF patients, members of the Bcc revert from a mucoid to a non-mucoid phenotype, suggesting a role for EPS in initial persistence, and that a loss of mucoidy may lead to increased virulence. Bcc LPS has previously been shown to be constitutively modified with 4-amino-4-deoxy-β-L-arbinoase (L-Ara4N). The enzymes involve din L-Ara4N biosynthesis were recently shown to be essential for B. cenocepacia viability. In this study, UDP-glucose dehydrogenase (Ugd) and 4-amino-4-deoxy-β-L-arbinose transferase (ArnT), the first and last enzymes of the biosynthetic pathway, were investigated. The L-Ara4N biosynthetic enzymes may be an Achilles’ heel of B. cenocepacia. Inhibitors to any of the enzymes in the L-Ara4N biosynthetic pathway could potentially be used alone, or in combination with other antimicrobial agents that would, under normal conditions, not be able to penetrate the outer membrane.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.641350  DOI: Not available
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