New venues for antibiotics

A reptile inspires the design of a new antimicrobial agent.

Go to the profile of Alyaa Mohamed
Apr 21, 2017
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New venues for antibiotics

Article highlights

  • A new synthetic antimicrobial peptide (AMP), DRGN-1, is designed based on a naturally occurring AMP (VK52) in the blood of a lizard found in Indonesia.
  • DRGN-1 demonstrates antimicrobial, antibiofilm, wound clearance and healing activities both in vitro and in vivo mouse models.
  • The study promotes the use of naturally occurring AMPs to inspire the synthesis of new drug molecules that could serve to treat various human diseases

Looks like there is an emerging solution for the problem of running out of antibiotics ! A recent study that appeared in npj biofilms and microbes introduces a synthetic antimicrobial peptide (AMP) based on a naturally occurring AMP in the plasma of a reptile. The Komodo dragon (Varanus komodoensis), from which the VK52 AMP is extracted, is a large species of lizard found on the Indonesian island of Komodo. Interestingly, the synthetic peptide is the result of rearrangement of only two amino acids at the N-terminal of the original peptide. The newly synthesized peptide, which the authors called DRGN-1, showed antimicrobial and antibiofilm activities against both Gram-negative and Gram-positive bacteria, even when mixed together. In demonstration of the direct applicability of the antimicrobial and antibiofilm properties of DRGN-1, the authors have also tested the efficacy of DRGN-1 in treating infected wounds in mouse models where DRGN-1 didn’t only clear the infection but also promoted wound healing by inducing keratinocyte (skin) cell migration.

This study opens a vast venue for where to look for pharmaceuticals and potential drug molecules, rather than depending only on natural products from plants or corals as starting molecules for drugs. Natural products are now expandable to encompass everything that comes from nature including products from wild-life.

So expect more venues for antibiotics and antimicrobials, just look with a careful eye and nature might give you some clues.

Komodo dragon-inspired synthetic peptide DRGN-1 promotes wound-healing of a mixed-biofilm infected wound

Abstract

Cationic antimicrobial peptides are multifunctional molecules that have a high potential as therapeutic agents. We have identified a histone H1-derived peptide from the Komodo dragon (Varanus komodoensis), called VK25. Using this peptide as inspiration, we designed a synthetic peptide called DRGN-1. We evaluated the antimicrobial and anti-biofilm activity of both peptides against Pseudomonas aeruginosa and Staphylococcus aureus. DRGN-1, more than VK25, exhibited potent antimicrobial and anti-biofilm activity, and permeabilized bacterial membranes. Wound healing was significantly enhanced by DRGN-1 in both uninfected and mixed biofilm (Pseudomonas aeruginosa and Staphylococcus aureus)-infected murine wounds. In a scratch wound closure assay used to elucidate the wound healing mechanism, the peptide promoted the migration of HEKa keratinocyte cells, which was inhibited by mitomycin C (proliferation inhibitor) and AG1478 (epidermal growth factor receptor inhibitor). DRGN-1 also activated the EGFR-STAT1/3 pathway. Thus, DRGN-1 is a candidate for use as a topical wound treatment. Wound infections are a major concern; made increasingly complicated by the emerging, rapid spread of bacterial resistance. The novel synthetic peptide DRGN-1 (inspired by a peptide identified from Komodo dragon) exhibits pathogen-directed and host-directed activities in promoting the clearance and healing of polymicrobial (Pseudomonas aeruginosa & Staphylococcus aureus) biofilm infected wounds. The effectiveness of this peptide cannot be attributed solely to its ability to act upon the bacteria and disrupt the biofilm, but also reflects the peptide’s ability to promsote keratinocyte migration. When applied in a murine model, infected wounds treated with DRGN-1 healed significantly faster than did untreated wounds, or wounds treated with other peptides. The host-directed mechanism of action was determined to be via the EGFR-STAT1/3 pathway. The pathogen-directed mechanism of action was determined to be via anti-biofilm activity and antibacterial activity through membrane permeabilization. This novel peptide may have potential as a future therapeutic for treating infected wounds.

Reference

Ezra M.C. Chung, Scott N. Dean, Crystal N. Propst, Barney M. Bishop & Monique L. van Hoek (2017) Komodo dragon-inspired synthetic peptide DRGN-1 promotes wound-healing of a mixed-biofilm infected wound. npj Biofilms and Microbiomes 3, Article number: 9 (2017).

Image credit: Hans Splinter on Flickr used under Creative Commons (CC BY-ND 2.0)

Go to the profile of Alyaa Mohamed

Alyaa Mohamed

PhD student, King Abdullah University of Science and Technology

I am a PhD student at the Computational Bioscience Research Centre (CBRC) at King Abdullah University of Science and Technology (KAUST) in Saudi Arabia. I am interested in using open source data to understand human infectious diseases. My research interests is mainly in systems biology of infectious agents and how they interact with the infected hosts.

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