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A biosynthetic strategy for re-engineering the Staphylococcus aureus cell wall with non-native small molecules.

Abstract：

:Staphylococcus aureus (S. aureus) is a Gram-positive bacterial pathogen that has emerged as a major public health threat. Here we 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. Thus, 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.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Nelson JW,Chamessian AG,McEnaney PJ,Murelli RP,Kazmierczak BI,Spiegel DA

doi

10.1021/cb100195d

subject

Has Abstract

pub_date

2010-12-17 00:00:00

pages

1147-55

issue

12

eissn

1554-8929

issn

1554-8937

journal_volume

5

pub_type

杂志文章

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