(October 8, 2010) -- Yale University researchers have covalently re-engineered the cell wall of Staphylococcus aureus, the most common cause of a staph infection. James W. Nelson†, Alexander G. Chamessian†, Patrick J. McEnaney†, Ryan P. Murelli†, Barbara I. Kazmiercak‡, and David A. Spiegel†* † Department of Chemistry, Yale University and ‡ Department of Medicine (Infectious Diseases), Section of Microbial Pathogenesis, Yale University School of Medicine, published the research findings in American Chemical Society's Journal of Chemical Biology, "A Biosynthetic Strategy for Re-engineering the Staphylococcus aureus Cell Wall with Non-native Small Molecules."
From the article abstract:
Staphylococcus aureus (S. aureus) is a Gram-positive bacterial pathogen that has emerged as a major public health threat. The Yale University authors report that the cell wall of S. aureus can be covalently re-engineered to contain non-native small molecules. This process makes use of endogenous levels of the bacterial enzyme sortase A (SrtA), which ordinarily functions to incorporate proteins into the bacterial cell wall.
Incubation of wild-type bacteria with rationally designed SrtA substrates results in covalent incorporation of functional molecular handles (fluorescein, biotin, and azide) into cell wall peptidoglycan. These conclusions are supported by data obtained through a variety of experimental techniques (epifluorescence and electron microscopy, biochemical extraction, and mass spectrometry), and cell-wall-incorporated azide was exploited as a chemical handle to perform an azide–alkyne cycloaddition reaction on the bacterial cell surface.
This report represents the first example of cell wall engineering of S. aureus or any other pathogenic Gram-positive bacteria and has the potential for widespread utility.
Staph infections are a major health risk globally, which has motivated other nanotech scientists to develop ZnO nanoparticle-based multilayer nanocomposite films that exhibit antimicrobial activity against Staphylococcus aureus bacteria.
A Biosynthetic Strategy for Re-engineering the Staphylococcus aureus Cell Wall with Non-native Small Molecules, DOI: 10.1021/cb100195d, Publication Date (Web): October 5, 2010, Copyright 2010 American Chemical Society, can be accessed here: http://pubs.acs.org/doi/abs/10.1021/cb100195d
* Corresponding author, [email protected].