Publications
2020
André Christophe, Veillard Florian, Wolff Philippe, Lobstein Anne-marie, Compain Guillaume, Monsarrat Clément, Reichhart Jean-marc, Noûs Camille, Burnouf Dominique, Guichard Gilles, Wagner Jerome
Antibacterial activity of a dual peptide targeting the Escherichia coli sliding clamp and the ribosome Journal Article
In: RSC Chemical Biology, vol. 1, no. 3, pp. 137-147, 2020.
Abstract | Links | BibTeX | Tags: Antibacterial, Antimicrobial peptides, Bacterial, clamp, E. coli, M3i, reichhart
@article{veillard2020,
title = {Antibacterial activity of a dual peptide targeting the Escherichia coli sliding clamp and the ribosome},
author = {Christophe André and Florian Veillard and Philippe Wolff and Anne-marie Lobstein and Guillaume Compain and Clément Monsarrat and Jean-marc Reichhart and Camille Noûs and Dominique Burnouf and Gilles Guichard and Jerome Wagner },
url = {https://pubs.rsc.org/en/content/articlelanding/2020/CB/D0CB00060D#!divAbstract},
doi = {10.1039/D0CB00060D},
year = {2020},
date = {2020-07-16},
journal = {RSC Chemical Biology},
volume = {1},
number = {3},
pages = {137-147},
abstract = {The bacterial processivity factor, or sliding clamp (SC), is a target of choice for new antibacterial drugs development. We have previously developed peptides that target Escherichia coli SC and block its interaction with DNA polymerases in vitro. Here, one such SC binding peptide was fused to a Proline-rich AntiMicrobial Peptide (PrAMP) to allow its internalization into E. coli cells. Co-immunoprecipitation assays with a N-terminally modified bifunctional peptide that still enters the bacteria but fails to interact with the bacterial ribosome, the major target of PrAMPs, demonstrate that it actually interacts with the bacterial SC. Moreover, when compared to SC non-binding controls, this peptide induces a ten-fold higher antibacterial activity against E. coli, showing that the observed antimicrobial activity is linked to SC binding. Finally, an unmodified bifunctional compound significantly increases the survival of Drosophila melanogaster flies challenged by an E. coli infection. Our study demonstrates the potential of PrAMPs to transport antibiotics into the bacterial cytoplasm and validates the development of drugs targeting the bacterial processivity factor of Gram-negative bacteria as a promising new class of antibiotics.},
keywords = {Antibacterial, Antimicrobial peptides, Bacterial, clamp, E. coli, M3i, reichhart},
pubstate = {published},
tppubtype = {article}
}
The bacterial processivity factor, or sliding clamp (SC), is a target of choice for new antibacterial drugs development. We have previously developed peptides that target Escherichia coli SC and block its interaction with DNA polymerases in vitro. Here, one such SC binding peptide was fused to a Proline-rich AntiMicrobial Peptide (PrAMP) to allow its internalization into E. coli cells. Co-immunoprecipitation assays with a N-terminally modified bifunctional peptide that still enters the bacteria but fails to interact with the bacterial ribosome, the major target of PrAMPs, demonstrate that it actually interacts with the bacterial SC. Moreover, when compared to SC non-binding controls, this peptide induces a ten-fold higher antibacterial activity against E. coli, showing that the observed antimicrobial activity is linked to SC binding. Finally, an unmodified bifunctional compound significantly increases the survival of Drosophila melanogaster flies challenged by an E. coli infection. Our study demonstrates the potential of PrAMPs to transport antibiotics into the bacterial cytoplasm and validates the development of drugs targeting the bacterial processivity factor of Gram-negative bacteria as a promising new class of antibiotics.