Jun 6, 2014
Understanding MRSA: a new tool for assessing antibacterial agents
MRSA, or the "superbug" methicillin-resistant Staphylococcus aureus, is responsible for a wide range of life-threatening hospital- and community-acquired infections that are often difficult to treat. New treatments are badly needed as the bacteria are adept at accumulating antibiotic resistance genes and exploit membrane-embedded proteins to their advantage. It has proven difficult to determine their spatial relationship, but reporting in Nanotechnology, researchers may have done just that.
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.
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.
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.
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.
About the author
Peter Taylor is Professor of Microbiology at the School of Pharmacy, University College London , UK. With a background in industrial and academic microbiology, his current interests include the development of new approaches to the treatment of bacterial infections, the pathogenesis of extra-intestinal Escherichia coli infections and the impact of the space environment on the behaviour of bacteria.