Affiliation:
1. Molecular Biophysics Unit (MBU) Indian Institute of Science Bangalore India
2. Department of Microbiology and Cell Biology Indian Institute of Science Bangalore India
3. School of Biology Indian Institute of Science Education and Research Thiruvananthapuram (IISER TVM) Thiruvananthapuram India
Abstract
AbstractThe 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.
Funder
Department of Biotechnology, Government of West Bengal
Ministry of Human Resource Development
Publisher
Springer Science and Business Media LLC
Subject
Genetics,Molecular Biology,Biochemistry
Cited by
4 articles.
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