MRSA bacteria are resistant to β-lactam antibiotics, our most important and effective class of antibacterial drugs that include the penicillins and cephalosprorins. This is due to the acquisition and dissemination of genes that encode a unique cell wall biosynthetic enzyme, PBP2a. This protein takes over the function of enzymes that are completely inhibited by these drugs. PBP2a works in tandem with PBP2 and other proteins of the staphylococcal "divisome", therefore it is beneficial to understand their relationship.

Extraction procedure

A multidisciplinary team from University College London and the universities of Birmingham, Sheffield and Warwick have taken advantage of a new technique for the extraction of membrane proteins and protein complexes. This preserves the functional and spatial characteristics of protein assemblages within the bilayer. The procedure uses the amphipathic polymer poly(styrene-co-maleic acid) to extract the proteins, along with their surrounding lipid environment, within discoidal nanoparticles, so that the membrane constituents can be investigated in their native state.

Widely applicable

The researchers show that PBP2 and PBP2a exist in the membrane in close physical proximity to FtsZ – a cytoskeletal protein that anchors the 20 or so components of the divisome at the site of bacterial cell division. Intriguingly, this observation raises the possibility that many, or perhaps all, divisome proteins can be extracted in this way as a single functional unit.

Dispersion

They investigate the impact of the naturally occurring polyphenol epicatechin gallate (ECg) on the physical association between PBP2 and PBP2a. When nanoparticles containing protein-lipid complexes from ECg-exposed MRSA membranes were examined, it was found that a proportion of the proteins were no longer in close physical proximity, strongly suggesting that ECg abrogates resistance by dispersing the co-functional components of the cell wall biosynthetic apparatus.

This technique provides a new tool for the assessment of antibacterial agents that compromise essential membrane-associated processes and provides a new approach to investigate membrane-embedded molecular machines in lipid bilayers.

More information can be found in the journal Nanotechnology 25 285101.

Further reading

Nanoparticles battle drug-resistant bacteria (Feb 2010)
AFM speeds up to film proteins (July 2012)