Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.742633
Title: Interactions within the tripartite drug-efflux pumps of gram-negative bacteria
Author: Marshall, Robert
ISNI:       0000 0004 7230 752X
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2018
Availability of Full Text:
Access from EThOS:
Access from Institution:
Abstract:
Antibiotic resistance, particularly amongst Gram-negative bacteria, has emerged as a major global concern. Working synergistically with the permeability barrier created by the cell envelope, multidrug efflux pumps contribute significantly to the intrinsic resistance of Gramnegative bacteria. Site-directed mutagenesis, informed by computational analyses, has been used on the prototypical tripartite efflux system, AcrAB-ToiC from Escherichia coli. Likely AcrA-ToiC interactions and functional roles of their sub-domains have been assessed using mutants in a combination of in vivo and in vitro approaches. Results indicate that both the tip region and the equatorial domain, halfway up the ToiC channel, are involved in determining the compatibility of AcrA with ToiC. On the other side of the interaction, both the tip region and the helices of the AcrA hairpin are essential for normal function. The hairpin tip is required to maintain the permeability barrier, while the helices are necessary for a stable AcrA-ToiC interaction. Combining these results with available literature, the first dynamic model of tripartite complex assembly is presented here. This model postulates initial bundling of AcrA and ToiC coiled-coil domains to open the ToiC channel followed by transition to a tip-to-tip interaction to drive channel closing and complex disassembly in an energy-dependent manner.
Supervisor: Not available Sponsor: Federation of European Microbiological studies (FEMS)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.742633  DOI: Not available
Keywords: QR Microbiology
Share: