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A CcdB toxin-derived peptide acts as a broad-spectrum antibacterial therapeutic in infected mice

Bhowmick, J and Nag, M and Ghosh, P and Rajmani, RS and Chatterjee, R and Karmakar, K and Chandra, K and Chatterjee, J and Chakravortty, D and Varadarajan, R (2023) A CcdB toxin-derived peptide acts as a broad-spectrum antibacterial therapeutic in infected mice. In: EMBO Reports .

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Official URL: https://doi.org/10.15252/embr.202255338


The bacterial toxin CcdB (Controller of Cell death or division B) targets DNA Gyrase, an essential bacterial topoisomerase, which is also the molecular target for fluoroquinolones. Here, we present a short cell-penetrating 24-mer peptide, CP1-WT, derived from the Gyrase-binding region of CcdB and examine its effect on growth of Escherichia coli, Salmonella Typhimurium, Staphylococcus aureus and a carbapenem- and tigecycline-resistant strain of Acinetobacter baumannii in both axenic cultures and mouse models of infection. The CP1-WT peptide shows significant improvement over ciprofloxacin in terms of its in vivo therapeutic efficacy in treating established infections of S. Typhimurium, S. aureus and A. baumannii. The molecular mechanism likely involves inhibition of Gyrase or Topoisomerase IV, depending on the strain used. The study validates the CcdB binding site on bacterial DNA Gyrase as a viable and alternative target to the fluoroquinolone binding site.

Item Type: Journal Article
Publication: EMBO Reports
Publisher: John Wiley and Sons Inc
Additional Information: The copyright for this article belongs to John Wiley and Sons Inc.
Keywords: antibacterial peptide; CcdB toxin; Gyrase and Topoisomerase IV as drug targets; mice models of infection; pathogenic bacteria
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 15 Jun 2023 08:10
Last Modified: 15 Jun 2023 08:10
URI: https://eprints.iisc.ac.in/id/eprint/81976

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