Biochemical and biophysical studies on SilE from the sil silver resistance locus

Asiani, Karishma (2017) Biochemical and biophysical studies on SilE from the sil silver resistance locus. PhD thesis, University of Nottingham.

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Abstract

Metal ions such as silver (Ag+), mercury (Hg2+), zinc (Zn2+) and copper (Cu+/Cu2+) have a long history of antimicrobial usage and some, such as Cu+/Cu2+, Ag+ and Zn2+ compounds are still used as antimicrobials. Prior to the introduction of antibiotics, Ag+ was arguably the most important antimicrobial and with the rapid emergence of antibiotic resistance, interest in Ag+ and its compounds as alternative antimicrobials have recently been revived. However, resistance to Ag+-based compounds has been emerging, with initial reports of carriage of silver resistance on a Salmonella enetrica serovar Typhimurium multi-resistance plasmid pMG101 isolated from burns patients in 1975. The proposed model for the mechanism of Ag+ resistance encoded by the sil genes from pMG101 involves export of Ag+ ions via an ATPase (SilP), an RND family effluxer (SilCFBA) and a periplasmic chaperone of Ag+ (SilE).

SilE is a periplasmic protein predicted to be intrinsically disordered until it binds Ag+ ions. This hypothesis was tested using structural and biophysical studies which showed that SilE is an intrinsically disordered and unstructured protein in its free apo-form, but folds to a compact, defined structure upon optimal binding of six Ag+ ions in its holo-form. Sequence analyses and site-directed mutagenesis established the importance of histidine and methionine containing motifs for Ag+-binding, and identified a nucleation core that initiates Ag+-mediated folding of SilE. The data show that SilE is a molecular metal sponge absorbing up to a maximum of eight Ag+ ions.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Scott, David
Soultanas, Panos
Hobman, Jon
Subjects: Q Science > QD Chemistry > QD241 Organic chemistry
R Medicine > RM Therapeutics. Pharmacology
Faculties/Schools: UK Campuses > Faculty of Science > School of Biosciences
UK Campuses > Faculty of Science > School of Chemistry
Item ID: 39567
Depositing User: Asiani, Karishma
Date Deposited: 25 Aug 2017 13:24
Last Modified: 25 Aug 2017 13:34
URI: http://eprints.nottingham.ac.uk/id/eprint/39567

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