Targeting Synthesis of the Chromosome Replication Initiator Protein DnaA by Antisense PNA-peptide Conjugates in

Overview

Journal Front Antibiot

Date 2025 Jan 16

PMID 39816250

Authors

Christopher Campion

Godefroid Charbon

Peter E Nielsen

Anders Lobner-Olesen

Affiliations

Soon will be listed here.

Abstract

Initiation of chromosome replication is an essential stage of the bacterial cell cycle that is controlled by the DnaA protein. With the aim of developing novel antimicrobials, we have targeted the initiation of DNA replication, using antisense peptide nucleic acids (PNAs), directed against DnaA translation. A series of anti-DnaA PNA conjugated to lysine-rich bacterial penetrating peptides (PNA-BPPs) were designed to block DnaA translation. These anti-DnaA PNA-BPPs inhibited growth of wild-type cells at low micromolar concentrations, and cells exposed to anti-DnaA PNA-BPPs exhibited characteristic hallmarks of chromosome replication inhibition. These results present one of very few compounds successfully targeting initiation of chromosome replication, an essential step in the bacterial cell cycle.

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