An article in one of Nature’s associated magazines called Biofilm and Microbiomes (B&M) caught my eye; “Komodo dragon-inspired synthetic peptide DRGN-1 promotes wound-healing of a mixed-biofilm infected wound”1. What a catchy title?!
The Komodo dragon (Varanus komodoensis) is a massive monitor lizard found on only five islands in Indonesia; Komodo, Rinca, Flores, Gili Motang, and Padar. They grow up to 3 metres long and weigh about 70kg. They have been around for millions of years, a bit like alligators and crocodiles, but are much more dinosaur like than these. They are also capable of short sprints up to 20mph and that’s nearly as fast as Usain Bolt. How do I know all this? I’ve been to Komodo and Rinca to see Komodo dragons and they are amazing.
Komodo dragons have about 80 different bacteria in their mouth and many are particularly good at causing sepsis. In fact this is thought to be the way Komodo dragons kill their pray. They have a small amount of venom which after they bite damages local tissue at the site allowing all of those nasty bacteria into the victim which eventually succumbs over the next few days… apparently they have a particularly unpleasant type of Pasteurella multocida a bit like cats and other carnivores.
So if Komodo dragons have such nasty bacteria in their mouths why do these bacteria not harm the dragon? It turns out that Komodo dragon saliva contains antimicrobial peptides which help to protect the dragon… it would be a pretty poor evolutionary development for an animal to die if it bit its own tongue wouldn’t it?
Enter the dragon; DRGN-1
DRGN-1 (derived from dragon) is the synthetic peptide produced by the authors of the B&M paper based upon a peptide from the saliva of the Komodo dragon, VK25 (VK from the dragon’s latin name Varanus komodoensis). I have no idea how they collected saliva from a Komodo dragon but I bet it was exciting! The modification of a couple of amino acids in VK25 enhanced the antimicrobial properties of DRGN-1 making it a better candidate for study.
How does DRGN-1 work?
DRGN-1 is a cationic antimicrobial peptide which has bactericidal activity through disruption of the bacterial cell membrane causing increased permeability and depolarisation resulting in rapid bacterial cell death. It is thought that DRGN-1 also has an activity inside the cell as well but this is yet to be properly described. So far DRGN-1 has shown activity against both Staphylococcus aureus and Pseudomonas aeruginosa in laboratory studies. It is thought that the antimicrobial activity of peptides like DRGN-1 might display antibacterial, antiviral and antifungal activity all at the same time.
It is hypothesised that it would be difficult for resistance to DRGN-1 to evolve naturally in bacteria due to the multiple mechanisms of action which would all need to be prevented at the same time for a bacterium to survive. Unfortunately it appears that there are already naturally occurring bacteria which are resistant to DRGN-1 including Francisella novicida and Burkholderia thailandensis… goodness knows where you might find these in nature but I’ve never seen them as human pathogens.
Another potential benefit to the use of DRGN-1 in the treatment of infections is its ability to prevent biofilm formation. Biofilms are essentially “slime cities” of bacteria which are relatively more resistant to antibiotics and therefore more difficult to treat. Biofilms are commonly found on infected prosthetic material and are one of the main reasons why infected prosthetics need to be removed. DRGN-1 has been shown to be able to prevent biofilm formation in the laboratory which might make it useful in treating infections where biofilm formation is a problem e.g. prosthetic joint infection, central venous catheter infection, urinary catheter infection.
DRGN-1 has also been shown to promote wound healing through a mechanism on keratinocytes (skin cells) which makes these cells migrate into wounds leading to enhanced healing. As a result DRGN-1 would be an ideal candidate for treating skin and soft tissue infections.
Does DRGN-1 make wounds heal better?
So far DRGN-1 has only been investigated in animal studies. In a mouse model of an infected wound with mixed S. aureus and P. aeruginosa, all wounds treated with DRGN-1 had healed by day 11 compared to none of the control wounds. Currently the only oral option we would have is to use PO Ciprofloxacin over the same time period. However, Ciprofloxacin is the main risk factor for Clostridium difficile, MRSA and multiple-antibiotic resistant Gram-negative bacteria.
So whilst it is still in the early stages of evaluation it is possible that DRGN-1 or something based upon it will eventually be available to treat skin and soft tissue infections. The initial results are promising but there is still a very long way to go before I might be recommending Komodo dragon spit as a treatment option, but you never know!
It has got me thinking though. What other animals might be a source of naturally occurring antibiotics. Cat saliva is said to have antimicrobial properties (and like Komodo dragons they have Pasteurella multocida in their normal mouth flora), and it’s no secret that I like cats (I have five domestic moggies at home!) so maybe I should start to study cat saliva… lions, tigers, jaguars, cheetahs, servals (but maybe not at home!)… if only I could….
1. Komodo dragon-inspired synthetic peptide DRGN-1 promotes wound-healing of a mixed-biofilm infected wound. Chung E, Dean S, Propst C et al Biofilms and Microbiomes 2017, 3:9 published online 11 April 2017