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The cathelicidin-derived close-to-nature peptide D-11 sensitises Klebsiella pneumoniae to a range of antibiotics in vitro, ex vivo and in vivo. | LitMetric

The cathelicidin-derived close-to-nature peptide D-11 sensitises Klebsiella pneumoniae to a range of antibiotics in vitro, ex vivo and in vivo.

Int J Antimicrob Agents

Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747 AG Groningen, the Netherlands. Electronic address:

Published: November 2021

AI Article Synopsis

  • The outer membrane of Gram-negative bacteria acts as a barrier, making it difficult for certain antibiotics to be effective and leading to high antibiotic tolerance.
  • Combining antibiotics with outer membrane-perturbing drugs, specifically cationic peptides like D-11, shows promise for overcoming this resistance.
  • D-11 demonstrated strong synergistic effects with various antibiotics against Klebsiella pneumoniae in different testing models, making it a viable candidate for enhancing the effectiveness of existing antibiotics.

Article Abstract

The outer membrane of Gram-negative bacteria constitutes a permeability barrier that prevents certain antibiotics reaching their target, thus conferring a high tolerance to a wide range of antibiotics. Combined therapies of antibiotics and outer membrane-perturbing drugs have been proposed as an alternative treatment to extend the use of antibiotics active against Gram-positive bacteria to Gram-negative bacteria. Among the outer membrane-active compounds, the outer membrane-permeabilising peptides play a prominent role. They form a group of small cationic and amphipathic molecules with the ability to insert specifically into bacterial membranes, inducing their permeabilisation and/or disruption. Here we assessed the combined effect of several compounds belonging to the main antibiotic families and the cathelicidin close-to-nature outer membrane peptide D-11 against four clinically relevant Gram-negative bacteria. The results showed that peptide D-11 displays strong synergistic activity with several antibiotics belonging to different families, in particular against Klebsiella pneumoniae, even better than some other outer membrane-active peptides that are currently in clinical trials, such as SPR741. Notably, we observed this activity in vitro, ex vivo in a newly designed bacteraemia model, and in vivo in a mouse abscess infection model. Overall, our results suggest that D-11 is a good candidate to repurpose the activity of traditional antibiotics against K. pneumoniae.

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Source
http://dx.doi.org/10.1016/j.ijantimicag.2021.106434DOI Listing

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