Incorporation of a Valine-Leucine-Lysine-Containing Substrate in the Bacterial Cell Wall.
Bioconjug Chem
; 27(10): 2418-2423, 2016 Oct 19.
Article
em En
| MEDLINE
| ID: mdl-27611478
ABSTRACT
The emergence of antibiotic-resistant bacteria is a major public health threat, and therefore novel antimicrobial targets and strategies are urgently needed. In this regard, cell-wall-associated proteases are envisaged as interesting antimicrobial targets due to their role in cell wall remodeling. Here, we describe the discovery and characteristics of a protease substrate that is processed by a bacterial cell-wall-associated protease. Stationary-phase grown Gram-positive bacteria were incubated with fluorogenic protease substrates, and their cleavage and covalent incorporation into the cell wall was analyzed. Of all of the substrates used, only one substrate, containing a valine-leucine-lysine (VLK) motif, was covalently incorporated into the bacterial cell wall. Linkage of the VLK-peptide substrate appeared unrelated to sortase A and B activity, as both wild-type and sortase A and B knock out Staphylococcus aureus strains incorporated this substrate into their cell wall with comparable efficiency. Additionally, the VLK-peptide substrate showed significantly higher incorporation in the cell wall of VanA-positive Enterococcus faecium strains than in VanB- and vancomycin-susceptible isolates. In conclusion, the VLK-peptide substrate identified in this study shows promise as a vehicle for targeting antimicrobial compounds and diagnostic contrast agents to the bacterial cell wall.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Parede Celular
/
Bactérias Gram-Positivas
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Bioconjug Chem
Ano de publicação:
2016
Tipo de documento:
Article