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Article Dans Une Revue RSC Chemical Biology Année : 2020

Antibacterial activity of a dual peptide targeting the Escherichia coli sliding clamp and the ribosome

Résumé

The bacterial processivity factor, or sliding clamp (SC), is a target of choice for new antibacterial drugsdevelopment. We have previously developed peptides that targetEscherichia coliSC and block itsinteraction with DNA polymerasesin vitro. Here, one such SC binding peptide was fused to a Proline-rich AntiMicrobial Peptide (PrAMP) to allow its internalization intoE. colicells. Co-immunoprecipitationassays with a N-terminally modified bifunctional peptide that still enters the bacteria but fails to interactwith the bacterial ribosome, the major target of PrAMPs, demonstrate that it actually interacts with thebacterial SC. Moreover, when compared to SC non-binding controls, this peptide induces a ten-foldhigher antibacterial activity againstE. coli, showing that the observed antimicrobial activity is linked toSC binding. Finally, an unmodified bifunctional compound significantly increases the survival ofDrosophilamelanogasterflies challenged by anE. coliinfection. Our study demonstrates the potential of PrAMPs totransport antibiotics into the bacterial cytoplasm and validates the development of drugs targeting thebacterial processivity factor of Gram-negative bacteria as a promising new class of antibiotics.

Domaines

Biotechnologies
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Dates et versions

hal-02905727 , version 1 (15-09-2020)

Identifiants

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Christophe André, Florian Veillard, Philippe Wolff, Anne-Marie Lobstein, Guillaume Compain, et al.. Antibacterial activity of a dual peptide targeting the Escherichia coli sliding clamp and the ribosome. RSC Chemical Biology, 2020, ⟨10.1039/D0CB00060D⟩. ⟨hal-02905727⟩
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