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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.

Titel:	A CcdB toxin-derived peptide acts as a broad-spectrum antibacterial therapeutic in infected mice.
Autor/in / Beteiligte Person:	Bhowmick, J ; Nag, M ; Ghosh, P ; Rajmani, RS ; Chatterjee, R ; Karmakar, K ; Chandra, K ; Chatterjee, J ; Chakravortty, D ; Varadarajan, R
Link:	Full Text Finder (Volltext)
Zeitschrift:	EMBO reports, Jg. 24 (2023-07-05), Heft 7, S. e55338
Veröffentlichung:	2024- : [London] : Nature Publishing Group ; <i>Original Publication</i>: Oxford, UK : Published for EMBO by Oxford University Press, 2000-, 2023
Medientyp:	academicJournal
ISSN:	1469-3178 (electronic)
DOI:	10.15252/embr.202255338
Schlagwort:	Animals Mice DNA Gyrase chemistry DNA Gyrase genetics DNA Gyrase metabolism DNA Topoisomerase IV genetics DNA Topoisomerase IV metabolism DNA Topoisomerase IV pharmacology Peptides pharmacology Staphylococcus aureus genetics Staphylococcus aureus metabolism Anti-Bacterial Agents pharmacology
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(PMID: 28446609) Grant Information: Department of Biotechnology, Ministry of Science and Technology, India - Indian Institute of Science (DBT-IISc) partnership program; BT/COE/34/SP15219/2015 Department of Biotechnology, Ministry of Science and Technology, India; DT.20/11/2015 Department of Biotechnology, Ministry of Science and Technology, India; Department of Science and Technology, Ministry of Science and Technology, India (DST FIST); Ministry of Education, India (MHRD); University Grants Commission, Ministry of Education, India (UGC Centre for Advanced Studies) Contributed Indexing: Keywords: CcdB toxin; Gyrase and Topoisomerase IV as drug targets; antibacterial peptide; mice models of infection; pathogenic bacteria Substance Nomenclature: 0 (Anti-Bacterial Agents) ; EC 5.99.1.3 (DNA Gyrase) ; EC 5.99.1.- (DNA Topoisomerase IV) ; 0 (Peptides) Entry Date(s): Date Created: 20230511 Date Completed: 20230710 Latest Revision: 20240512 Update Code: 20240512 PubMed Central ID: PMC10328072

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