AUTHOR=Campion Christopher , Charbon Godefroid , Nielsen Peter E. , Løbner-Olesen Anders 

TITLE=Targeting synthesis of the Chromosome Replication Initiator Protein DnaA by antisense PNA-peptide conjugates in Escherichia coli

JOURNAL=Frontiers in Antibiotics

VOLUME=3

YEAR=2024

URL=https://www.frontiersin.org/journals/antibiotics/articles/10.3389/frabi.2024.1384390

DOI=10.3389/frabi.2024.1384390

ISSN=2813-2467

ABSTRACT=<p>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 <italic>Escherichia coli</italic> 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.</p>