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Characterisation of the selective binding of antibiotics vancomycin and teicoplanin by the VanS receptor regulating type A vancomycin resistance in the enterococci

DOI: 10.1016/j.bbagen.2017.05.011 DOI Help

Authors: C. S. Hughes (Diamond Light Source; University of Central Lancashire) , E. Longo (Diamond Light Source) , M. K. Phillips-Jones (University of Central Lancashire) , R. Hussain (Diamond Light Source)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Biochimica Et Biophysica Acta (bba) - General Subjects

State: Published (Approved)
Published: May 2017
Diamond Proposal Number(s): 14484 , 12003 , 10310 , 4986 , 9016 , 5056

Open Access Open Access

Abstract: A-type resistance towards “last-line” glycopeptide antibiotic vancomycin in the leading hospital acquired infectious agent, the enterococci, is the most common in the UK. Resistance is regulated by the VanRASA two-component system, comprising the histidine sensor kinase VanSA and the partner response regulator VanRA. The nature of the activating ligand for VanSA has not been identified, therefore this work sought to identify and characterise ligand(s) for VanSA. In vitro approaches were used to screen the structural and activity effects of a range of potential ligands with purified VanSA protein. Of the screened ligands (glycopeptide antibiotics vancomycin and teicoplanin, and peptidoglycan components N-acetylmuramic acid, D-Ala-D-Ala and Ala-D-y-Glu-Lys-D-Ala-D-Ala) only glycopeptide antibiotics vancomycin and teicoplanin were found to bind VanSA with different affinities (vancomycin 70 μM; teicoplanin 30 and 170 μM), and were proposed to bind via exposed aromatic residues tryptophan and tyrosine. Furthermore, binding of the antibiotics induced quicker, longer-lived phosphorylation states for VanSA, proposing them as activators of type A vancomycin resistance in the enterococci.

Journal Keywords: Maximum 6 key words: vancomycin; teicoplanin; antibiotic resistance; enterococci; circular dichroism; fluorescence

Diamond Keywords: Bacteria

Subject Areas: Biology and Bio-materials, Medicine

Diamond Offline Facilities: Membrane Protein Laboratory (MPL)
Instruments: B23-Circular Dichroism

Added On: 17/05/2017 09:46


Discipline Tags:

Pathogens Antibiotic Resistance Infectious Diseases Health & Wellbeing Biophysics Life Sciences & Biotech

Technical Tags:

Spectroscopy Circular Dichroism (CD)