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Author:  Alyssa Walsh

Contributed to Toxipedia as part of the University Partnerships Program.


The Komodo dragon is the world’s largest lizard, with males typically weighing 150 pounds (90 kilograms) and growing up to 10 feet (3 meters) long (Bull JJ, Jessop TS, Whiteley M. 2010). These are carnivorous lizards that inhabit the Eastern Indonesian islands of Komodo, Flores, Rinca, and Gili Montang (Abrahamian, F. M., Goldstein, E. J.C. 2011). Komodo dragons will prey mostly on large, ungulate (hoofed mammal) animals. While hunting, if the lizard’s prey does not die from the attack, it will later meet its demise by a toxic exposure. The mechanism by which the Komodo dragon poisons its victims is a very controversial topic. For years, the consensus opinion was that the Komodo dragon’s prey ultimately died of bacterial infection, or sepsis; however, Dr. Fry and his team found a complex venom gland when performing a magnetic resonance image (MRI) on a deceased Komodo dragon. (Young, E. 2009).


Komodo dragons have been a toxicological mystery to scientists for many years. These gigantic lizards are becoming more and more understood, especially after the discovery of a complex venom gland found in 2009. This discovery likely will lead scientists to more information about the Komodo dragon’s way of life. 

Route of Toxin Exposure

If the prey escapes the initial trauma of a Komodo dragon bite, the animal will likely die later of envenomation. Some scientists believe a bacterial infection will occur after the dragon’s prey has been bitten through the subcutaneous layers of flesh. Others suggest evidence of a “bite and drip” mechanism for envenomation exists. This means that, despite not having the customary dental work of other venomous reptiles, the Komodo dragon excretes venom into an open wound from openings between the teeth.  This occurs during the initial attack. If the animal, usually water buffalo or Timor deer, is able to escape, the administered venom will likely poison, and thus kill, the animal.

Mode of Action

It is difficult to accurately explain the mode of action through which the Komodo dragon’s venom and/or bacteria kill. There has been research that shows over 50 different taxa of pathological organisms found in the mouth of a Komodo dragon (Mackessy, S. P. p. 70). Staphylococcus sp. are the most abundant bacteria species found in the mouth of Komodo dragons. Staphylococcus sp. is a Gram-positive bacterium that thrives in aerobic conditions. Specific species of Staphylococcus isolated from Komodo dragon saliva are Staphylococcus captis (cause of endocarditis), Staphylococcus caseolyticus (causes no human disease known), (Mackessy, S. P. p 70) and Staphylococcus aureus (cause of Methicillin-resistant Staphylococcus aureus, MRSA).  Pseudomonas aeruginoas (causes generalized inflammation and sepsis) was also isolated from Komodo dragon saliva. This bacterium is typically the cause of cavities and causes septicemia in mammals, yet seems to be the most effective in causing sepsis (Bull JJ, Jessop TS, Whiteley M. 2010). E. coli was also isolated from the mouth of some Komodo dragons (Abrahamian, F. M., Goldstein, E. J.C. 2011). While perhaps not surprising, there are many other bacterial species found in the mouths of Komodo dragons. This is probably the case since the dragons are carnivorous animals, and there is likely to be decaying flesh in their teeth. Unfortunately, this theory has been shown to be inconsistent because no two Komodo dragons have the same species of bacteria (Fry BG, Wroe S, Teeuwisse W, et al. 2009).

More recent findings have brought light to the potential presence of a complex mandibular venom gland with a total of six compartments—one major posterior compartment and five smaller anterior compartments. The complexity of this gland is seen in the excretion of venom between serrated teeth, instead of through hollow tubular fangs like most venomous reptiles. Five different toxin classes have been identified: AVIT proteins (named after the first amino terminal sequences in all these proteins: alanine, valine, isoleucine, and threonine), natriuretic peptide, type III phospholipase A2 protein scaffolds, and kallikrein (Fry BG, Wroe S, Teeuwisse W, et al. 2009). The proteins found in Komodo dragon venom are similar, if not identical, to many snake venoms (Zimmer, C. 2009). In the case of both the dragons and snakes, the mechanisms of many of these toxins are not well understood.

The AVIT protein class is made up of 80-90 amino acids, and ten of these amino acids are cysteine with equal spacing between each amino acid residue. The difference between proteins in the class is found near the carboxyl end of the molecule. This class of proteins has many functions such as contraction of the ilium and colon and hyperalgesia (increased sensitivity to pain), and can also be found in snake venoms and amphibian skin excretions, from which it was originally tested. The binding of AVIT proteins to G-protein coupled receptors activates signal transduction pathways. Prokineticin 1 and 2 are types of G-protein coupled receptors to which AVIT will bind.  These receptors are present in many tissues, including the central nervous system. The AVIT proteins stimulate the p44/p45 mirogen-activated protein kinase pathway and phosphinositide turnover. This activation may lead to cell division and migration, protection from apoptosis, and hyperalgesia—these are the result of intravenous injections. (Kaser A, Winklmayr M, Lepperdinger G, Kreil G. 2003).

Cysteine-rich secretory proteins (CRISPs) are not a well-understood class of toxins. Some of what is understood, however, relates to their ability to inhibit or block various ion channels. A list of these includes blocking of potassium and calcium currents in neurons, binding to cyclic nucleotide-gated ion channels in photoreceptors and olfactory neurons, and blockage of calcium ion release from the sarcoplasmic reticulum or cardiac and skeletal muscle. What is well known is the structure of the CRISPs (Mackessy, S. P. p.26). The number of functions of this protein suggests a separation between two domains on the molecule, which could potentially indicate how the molecule is able to have such a variety of effects. Functional separation is also seen in the multifunctional reptile venom, PLA2 enzymes. However, functional sites of CRISPs have not been fully determined (Mackessy, S. P p. 329). 

The kallikrein class of proteins is a serine protease group that is found in blood, saliva, and tissues of mammals. However, the kallikrein found in Komodo dragon venom is also found in snake and lizard venom. This enzyme releases the potent vasodepressor, bradykinin, through proteolytic activity (Evolution of Kallikrein-like enzymes in snakes and lizards. 2011). Kallikrein catalyzes the hydrolysis of internal peptide bonds in a polypeptide chain via a catalytic triad composed of a serine nucleophile activated by an acidic or basic proton relay. The specific kallikrein found in Komodo dragon venom is kallikrein toxin Var13 (Huntley RP, Sawford T, Mutowo-Muellenet P, Shypitsyna A, Bonilla C, Martin MJ, O'Donovan C. 2014.). 

Natriuretic peptides are another protein whose toxic mechanism is not well understood. Toxicity is induced through the inhibition of ion transfer of Na+ and K+ ion pumps.  Na+ is then unable to reabsorb back into the cells. The change in the body’s chemical gradient can cause vasodilation along with diuretic effects and natriuretic effects (Beckstorm, B., Nelston, K., Parker, S. 2013).

Phospholipase A2 enzymes (T-III) catalyze the hydrolysis of the sn-2 position of membrane glycerophospholipids to free fatty acids. These enzymes are Ca+ enzymes that have an active site histidine (Mackessy, S. P. p.174). This will cause a change in the body’s chemical make up and will cause anticoagulation.


As of early 2015, there is no known antivenin for Komodo dragon venom. This is because of the lack of specific and in-depth knowledge of Komodo dragon venom.  Another reason there is a lack of antivenin is due to the wide range of toxins and bacteria present in the saliva. The variation of the chemical makeup of the saliva between the dragons themselves differs significantly as well. This makes it difficult to create an antivenin that is specific enough to be effective against all Komodo dragon bites.

Health Effects

The various proteins found in the venom of the Komodo dragon causes a number of effects on mammals. The AVIT protein class has shown to cause strong constrictions of the intestinal smooth muscle, which results in hyperalgesia and cramping (Beckstorm, B., Nelston, K., Parker, S. 2013). CRISP toxins are the main cause of hypothermia (Fry BG, Wroe S, Teeuwisse W, et al. 2009). Kallikrein increases vascular permeability (causing hemorrhaging), hypotension (low blood pressure), and stimulated inflammation. Natriuretic peptides will cause a loss of consciousness, and PLA2 (T-III) will cause anticoagulation. Essentially, envenomation by Komodo dragons will cause a mammal to be immobilized (due to cramping), lose consciousness (due to low blood pressure), and massive blood loss (due to hemorrhaging). All of these symptoms generally occur, and this combination results in death.


Abrahamian, F. M., Goldstein, E. J.C. 2011. Microbiology of Animal Bite Wound Infections. Clinical Microbiology Reviews.

Beckstorm, B., Nelston, K., Parker, S. 2013. Natriuretic-type Toxin (Varanus komodoensis).

Bull JJ, Jessop TS, Whiteley M. 2010. Deathly Drool: Evolutionary and Ecological Basis of Septic Bacteria in Komodo Dragon Mouths. PLoS ONE 5.6

Evolution of Kallikrein-like enzymes in snakes and lizards. 2011. Bioinformatics2011.

Fry BG, Wroe S, Teeuwisse W, et al. 2009. A central role for venom in predation by Varanus komodoensis (Komodo Dragon) and the extinct giant Varanus (Megalania) priscus. Proceedings of the National Academy of Sciences of the United States of America.

Huntley RP, Sawford T, Mutowo-Muellenet P, Shypitsyna A, Bonilla C, Martin MJ, O'Donovan C. 2014. GO:0004252 serine-type endopeptidase activity. The GOA database: Gene Ontology annotation.

Kaser A, Winklmayr M, Lepperdinger G, Kreil G. 2003. The AVIT protein family: Secreted cysteine-rich vertebrate proteins with diverse functions. EMBO Report.

Mackessy, S. P. (Ed.). (2010). Handbook of Venoms and Toxins of Reptiles. Boca Raton, FL: CRC Press.

Young, E. 2009. Venomous Komodo dragons kill prey with wound-and-poison tactics. National Geographic.

Zimmer, C. 2009. Chemicals in Dragon’s Glands Stir Venom Debate. The New York Times.

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