National Physical Laboratory

Biophysical standards Biophysical standards for antimicrobial resistance

Establishing biophysical rationale for standards of microbial membrane resistance.

The challenge of antimicrobial resistance, which is notoriously associated with the emergence of 'superbugs', (methicillin-resistant Staphylococcus aureus, MRSA), refers to the failure of conventional antibiotics to treat bacterial infections.

Resistance to antibiotics is a natural selection process which occurs at the genetic level and can be sped up with their frequent use. More alarming is the emergence of 'superbugs' against last-resort polypeptide antibiotics that target bacterial membranes.

Resistant membranes incur formidable costs for bacteria to develop, but are possible (vancomycin resistant Staphylococcus aureus, VRSA). Generic biophysical factors that drive resistance development relate to lipid composition and lipid receptors, membrane thickness and permeability, peptide-lipid interactions and the like. However, there remains an unmet need for measurable reference points for antimicrobial membrane resistance.

Structures of membrane-active polypeptide antibiotics and SEM image of E. coli cells

(A) structures of membrane-active polypeptide antibiotics (1AA5, 1T5M, 3E7U PDB entries rendered with PyMol), (B) SEM image of E. coli cells with ruptured membranes.

This research aims to introduce biophysical standards of membrane resistance to support future reference materials and screening membrane platforms for new antibiotics. NPL scientists are developing quantitative biophysical measurements and molecular engineering together with comparative biophysical microbiology and microscopy analysis to relate microbial membrane composition and structure to microbial resistance, using commercial and emerging membrane-active and conventional antibiotics.

Relevant publications

Anti-antimicrobial peptides: coiled-coil-mediated host defense antagonism
Ryan L, Lamarre B, Diu T, Ravi J, Judge PJ, Temple A, Carr M, Cerasoli E, Su B, Jenkinson HF, Martyna G, Crain J, Watts A, Ryadnov MG
J Biol. Chem.
2013, 10.1074/jbc.M113.459560

Nanoscale imaging reveals laterally expanding antimicrobial pores in lipid bilayers
Rakowska PD, Jiang H, Ray S, Pyne A, Lamarre B, Carr M, Judge PJ, Ravi J, Gerling UIM, Koksch B, Martyna G, Hoogenboom BW, Watts A, Crain J, Grovenor CRM, Ryadnov MG
Proc. Natl. Acad. Sci. USA, 2013, 110, 8918-8923

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