What Does Spider Venom Do To Blood?

Spider venom reveals new secret: Once injected into a bite wound, venom of brown recluse spider causes unexpected reaction

Venom of the brown recluse spider causes a reaction in the body that is different from what researchers previously thought, a discovery that could lead to development of new treatments for spider bites.

University of Arizona researchers led a team that has discovered that venom of spiders in the genus Loxosceles, which contains about 100 spider species including the brown recluse, produces a different chemical product in the human body than scientists believed.

The finding has implications for understanding how these spider bites affect humans and for the development of possible treatments for the bites.

One of few common spiders whose bites can have a seriously harmful effect on humans, the brown recluse has venom that contains a rare protein that can cause a blackened lesion at the site of a bite, or a much less common, but more dangerous, systemic reaction in humans.

«This is not a protein that is usually found in the venom of poisonous animals,» said Matthew Cordes, an associate professor in the UA’s department of chemistry and biochemistry and member of the UA BIO5 Institute who led the study, published today in the journal PLOS ONE.

The protein, once injected into a bite wound, attacks phospholipid molecules that are the major component of cell membranes. The protein acts to cleave off the head portion of the lipids, leaving behind, scientists long have assumed, a simple, linear, headless lipid molecule.

The research team has discovered that in the test tube, the venom protein causes lipids to bend into a ring structure upon the loss of the head portion, generating a cyclical chemical product that is very different than the linear molecule it was assumed to produce.

«The very first step of this whole process that leads to skin and tissue damage or systemic effects is not what we all thought it was,» Cordes said.

The lipid knocks off its own head by making a ring within itself, prompted by the protein from the spider venom, Cordes explained. «Part of the outcome of the reaction, the release of the head group, is the same. So initially scientists believed that this was all that was happening, then that became established in the literature.»

The research team includes Cordes; Vahe Bandarian, an associate professor also in the UA’s department of chemistry and biochemistry; and Greta Binford, an associate professor of biology at Lewis and Clark College in Portland, Ore. who, completed her doctorate and a postdoc at the UA.

Cordes, Bandarian and Daniel Lajoie, a PhD candidate in Cordes’s lab, tested venom from three species of brown recluse spiders from North and South America. Binford, an arachnologist who has traveled the world in search of the eight-legged creatures, collected the spiders, isolated their DNA and milked their venom, which was then frozen and shipped to the UA labs for analysis.

«We didn’t find what we thought we were going to find,» Cordes added. «We found something more interesting.»

The cyclical shape of the headless molecule means that it has different chemical properties than the linear headless lipid believed to be generated by the protein, Cordes explained. The biological effects of either molecule in human membranes or insects aren’t completely known, he said, but they are likely to be very different.

«We think it’s something about that ring product generated by this protein that activates the immune system,» Binford said.

«The properties of this cyclic molecule aren’t well-known yet, but knowing that it’s being produced by toxins in venoms might heighten interest,» Cordes said. «Knowing how the protein is actually working and making this cyclic molecule could also lead to better insights on how to inhibit that protein.»

For those who do have a reaction to the venom, the most common response is inflammation that after one to two days can develop into a dark lesion surrounding the bite site. The blackening, or necrosis, of the skin is dead skin cells, evidence of the immune system’s efforts to prevent spread of the toxin by preventing blood flow to the affected area.

«Our bodies are basically committing tissue suicide,» Binford said. «That can be very minor to pretty major, like losing a big chunk of skin. The only treatment in that case is usually to have a skin graft done by a plastic surgeon.»

About once every five years, Binford said, someone develops a serious systemic reaction to a brown recluse bite, which can be fatal.

«If it goes systemic, then it can cause destruction of blood cells and various other effects that can in extreme cases lead to death by kidney failure or renal failure,» Cordes said.

However, it is believed that the vast majority of brown recluse bites are so minor that they go unnoticed by those who were bitten.

It’s not known what determines the type or severity of reaction a person is likely to get when bitten by a brown recluse, Cordes said, «but what is known is that this protein is the main cause of it.»

«I think if we know how the toxin works, it opens a new door to understanding how the syndrome is initiated as well as the possibility of blocking that process.»

«The discovery of this product may be crucial in understanding what exactly is going on in the human reaction,» Binford said.

For the spider biologists and chemists, the work has just begun.

«These spiders have been around with this toxin for over 120 million years,» Binford said. «I want to understand the full set of variation present in a single spider and across the entire genus and the activity of this compound.»

See also:  What Do Yellow Sac Spiders Eat?

«People think about the brown recluse with fear,» she added. «When I think about a brown recluse or any other spider, I think about how a single spider can have 1,000 chemicals in its venom and there are about 44,000 species, so tens of millions of unique compounds in spider venom that we’re in the process of discovering. We have a lot to learn about how these venom toxins work and potential for understanding new chemistry and developing new drugs or treatments.»

Understanding how brown recluse venom produces harmful effects in humans is particularly relevant in Arizona, a hotbed for these spiders, Cordes said: «There are more variant species of Loxosceles here than anywhere else in the United States.»

The UA-led study of brown recluse venom was supported initially by a pilot project award from the UA BIO5 Institute. Binford’s venom collections were supported by a National Science Foundation Career Award.

Story Source:

Materials provided by University of Arizona. Original written by Shelley Littin. Note: Content may be edited for style and length.

Journal Reference:

  1. Daniel M. Lajoie, Pamela A. Zobel-Thropp, Vlad K. Kumirov, Vahe Bandarian, Greta J. Binford, Matthew H. J. Cordes. Phospholipase D Toxins of Brown Spider Venom Convert Lysophosphatidylcholine and Sphingomyelin to Cyclic Phosphates. PLoS ONE, 2013; 8 (8): e72372 DOI: 10.1371/journal.pone.0072372

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Spider-Man: 5 Weird Effects of Real Spider Bites

Although Spider-Man got his superhero abilities from a spider bite, ordinary spider-bite victims may have to deal with spider-bite effects that have nothing to do with being able to scale walls and climb around on ceilings.

Some of the weirdest effects that spider venom may have on regular, nonsuperhero humans include unwanted erections, dead skin tissue that turns black, unusual rashes, dark pee and sweat so heavy it makes puddles on the floor.

However, it is important to remember that such unusual symptoms are extremely rare, and the vast majority of spider bites are harmless, or cause only mild irritation and itchiness. [In Photos: The Science of the Amazing Spider-Man 2]

In fact, spiders do not often bite people, and if they do, it is because they feel threatened. Black widow spiders and brown recluse spiders are the only two spider species in North America whose bites may sometimes result in symptoms more serious than minor local pain and swelling, according to Rick Vetter, a retired arachnologist at the University of California, Riverside.

Although hobo spiders, which are common in the Pacific Northwest, are also listed by the Centers for Disease Control and Prevention as one of the three types of spiders that can be toxic to people, some researchers have argued that hobo-spider venom may not be so toxic after all.

Here are some of the weirdest effects spider bites have had on people.

Venomous Viagra?

The Brazilian wandering spider’s venom contains a toxin whose unusual erection-inducing qualities have attracted the attention of the pharmaceutical industry. In 2007, researchers found that the bites of the Brazilian wandering spider can cause long and painful erections in human males, along with other symptoms. The effect happens because the spider’s venom raises the levels of nitric oxide, which is a chemical that increases blood flow.

Researchers have since tested the toxin that is responsible for this unusual effect, called PnTx2-6, in the hope of developing a potential new drug for erectile dysfunction.

The Brazilian wandering spider is large, with a body size reaching up to 2 inches (5 centimeters) and leg spans stretching 5 or 6 inches (13 to 15 cm). Although the creepy crawler’s size may make it look threatening, it is not aggressive and, like most spiders, will only attack when it feels threatened, experts say.

Dead tissue

Although there have been cases of «necrotic arachnidism,» in which spider venom kills human tissue, such cases are extremely rare. In fact, researchers estimate that less than one case of dead human tissue is reported per 5,000 spider bites from verified spider specimens, and verification of spider bites is very rare, Dr. Scott Weinstein, a toxinologist at Women’s and Children’s Hospital in North Adelaide, South Australia, told Live Science. (Toxinology is the study of the venoms and poisons of plants, animals and microbes; it is different from toxicology, which is the study of chemicals and drugs as they affect the body.)

See also:  How Many Spider Species Are There?

If a spider bite is «verified,» it means that there was actual evidence that a person was bitten by a particular kind of spider. The only spider in North America whose bites have been shown to kill human tissue in rare instances is the brown recluse spider, Vetter said.

When necrosis does occur, tissue may sometimes turn black as cells die. One such case was reported last year — a woman on vacation in Italy developed necrosis in her ear after being bitten by a brown recluse spider. Part of her ear turned black, and her doctor had to remove the dead tissue and restore it, using cartilage from the woman’s ribs.

Weird rash

Some people develop unpredictable skin reactions to spider bites. A 66-year-old patient in France developed a strange rash after being bitten by a spider, which the doctors suspected was likely a brown recluse spider, according to a report of his case. The man had pinhead-size bumps on his forearms, which later spread to other parts of his body.

The medical staff diagnosed the man with a condition called acute generalized exanthematous pustulosis (AGEP), which typically occurs in people taking antibiotics. Other reports have also linked AGEP to brown recluse spider bites, the researchers said. The man recovered in five days, after doctors treated him with oral corticosteroids.

Unusual blood disorders and dark pee

In the case of the man in France who developed the strange rash, the doctors also found that he had a blood disease called periarteritis nodosa (PAN), in which small arteries become swollen and damaged. The doctors linked his blood condition with the brown recluse bite, because previous reports had described conditions similar to PAN in animals injected with brown recluse spider venom.

In fact, blood disorders are some of the rare symptoms that occur in people who have been bitten by recluse spiders, Vetter wrote in one study. The brown recluse venom may cause red blood cells to burst and release their contents into plasma, in a process called hemolysis. As a result, anemia may develop and can last from four to seven days, he said.

These blood problems may lead to other symptoms, such as acute kidney injury and jaundice (yellowing of the skin), as the blood protein called hemoglobin breaks down. The waste products of the breakdown can build up in the blood, and turn the urine dark when they are then excreted.

Puddles of sweat

Some Australian widow spider bite victims have been found to sweat so much after getting bitten that their sweat formed puddles on the floor, Vetter reported in one study.

Excessive sweating is one of the symptoms that may result from the bites of certain spiders that affect the nervous system. The venom of the black widow, for instance, attacks nerves by blocking their signals to the muscles. This causes the muscles to contract repeatedly, which can be painful and stressful for the body.

Black widow spider bite victims may also experience other nerve-related symptoms, such as high blood pressure, restlessness and severe facial spasms.

Who gets these spider-bite symptoms?

Whether a spider bite affects a person only mildly or causes severe symptoms depends on a number of factors, such as the amount of the venom injected, and the size and age of the person who got bitten. Children and elderly people are particularly susceptible to extreme symptoms from toxic spider bites.

However, most people who get bitten are highly unlikely to experience these severe symptoms, researchers say.

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Spider bites and venoms

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Spider venoms are a cocktail of many chemicals.

Some are neurotoxins, which evolved to kill or immobilise arthropods like insects by attacking their nervous systems; others are cytotoxins which help break down the tissue so the spider can ingest a liquefied meal. Unfortunately, a few of these chemicals can be seriously toxic to people.

How does spider venom work in humans?

Venoms are chemicals of biological origin (i.e. made by an animal) used for the purpose of attack or defence. Venoms are made by specialised organs, such as modified salivary glands, and are delivered via specialised systems such grooved or hollow fangs. Most venoms consist of a complex mixture of chemical substances, including proteins, peptides, sugars and other substances. Venoms may affect many systems of the body. Common venom effects include paralysis, interference with blood clotting, breakdown of muscle, pain, breakdown of tissues and effects on the cardiorespiratory system (the heart and lungs).

There are basically two types of venom that have an effect on humans: neurotoxic and cytotoxic (or necrotic) venoms. Neurotoxic venoms work directly on the nervous system. The best known example is the venom of the Black Widow/Redback spiders (Latrodectus species). Necrotic venoms cause damage to the tissues, such as blisters and lesions. There are no confirmed records of spider bites in Australia causing necrotic lesions, although the bites of Recluse Spiders, which are native to the Americas, have been confirmed to cause tissue necrosis. Generally, neurotoxic venoms kill more quickly than cytotoxic venoms.

See also:  10 Biggest Spiders In The World

Toxins which attack nerves

The main effect of a neurotoxic venom is to block nerve impulses to the muscles, causing cramps and rigidity and also disrupting many of hte body’s functions. It also overstimulates the production of the neurotransmitters, acetylcholine and norephinephrine, causing paralysis of the entire nervous system. The combined effect causes sudden and severe stress to the entire human body. In extreme cases, this can result in death due to respiratory or circulatory failure. Funnel-web Spider venom — known as atraxotoxin — acts directly upon the nervous system in this way.

Toxins which attack the tissue

Necrotic venoms cause skin blisters around the site of the bite, which may lead to ulcers and tissue death — necrosis. Recent studies of confirmed spider bites suggest that, in Australia, these bites do not cause tissue necrosis. These sorts of symptoms are most likely due to other types of clinical conditions.

Making antivenoms

Antivenoms for spider toxins are produced by injecting horses, goats or rabbits with the spiders’ venom. This doesn’t harm these animals because they are either given only small venom doses or they have a naturally mild reaction to the venom. Antibody molecules are produced as a result of the reaction of the animal’s immune systems to the foreign venom molecules. These are used to make life-saving antivenoms for humans. Molecular research aimed at making synthetic antivenoms is in progress.

First aid — points to remember

  • Those at greatest risk, as with any toxin, are the very young or elderly and those with pre-existing cardiovascular disease.
  • Suspected funnel-web or mouse spider bites should always be treated as quickly as possible by applying a pressure bandage and immobilising the victim (do not cut the wound or apply a tight tourniquet).
  • Bandaging is not necessary for Redback Spider bites. Applying pressure worsens the pain that often comes with Redback bites.
  • The application of a cold pack may help if the bite is painful. For most spider bites, no other first aid is necessary.
  • Always seek medical attention for any suspected funnel-web, mouse or Redback Spider bite and for any other bite if symptoms develop or persist.
  • Catch the spider for positive identification if you can.

Pressure bandages and splints

Pressure bandages slow down the movement of venom into the bloodstream, which reduces the effect of the nerve toxins in the venom. Pressure bandages should only be used for funnel-web or mouse spider bites. When the spider bites someone, the venom is injected into the tissue under the skin. A pressure bandage slows down the movement of both tissue fluid and blood near the surface. This prevents the venom from rapidly reaching the bloodstream and is very effective treatment as long as the patient is kept still.

  1. Wind the bandage firmly around the bitten arm or leg starting from the bite. The bandage should not be so tight that it restricts blood flow.
  2. Wrap the entire limb, then apply a splint to prevent movement.
  3. Keep the victim as still as possible.
  4. Do not remove the bandage.
  5. Seek medical attention as soon as possible.

Catching a spider

  • Quickly place an empty jar over the spider
  • Push a stiff piece of card under the jar to cover its mouth
  • Up-end the jar so that the spider falls to the bottom
  • Quickly remove the card and securely replace the jar’s lid

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