Tarantulas and Their Venomous
Relatives
Poecilotheria metallica/ Zoological Survey of India
Jazlyn Mooney & Ann Stevenson
Introduction
• We chose to study tarantula venom due to its
broad spectrum of potential pharmaceutical
uses.
• During our research we noticed that many
large venomous spiders are commonly
mistaken as tarantulas, thus creating an
unnatural fear of tarantulas within the human
population.
Introduction
• What is venom?
• True Tarantulas
- The difference between Old World & New
World
- Potential uses and mechanism
- Case Studies
• Venom of Spiders Commonly Mistaken as
Tarantulas
- Potential uses and mechanisms
Introduction
• Envenomation
• Antivenin
• Newly Discovered Species
• Summary
• Conclusion
What is venom?
Poisonous fluid secreted by animals and
insects by typically injected into prey or
aggressors by biting or stinging.
TRUE TARANTULAS
Categorization
New
World
Old World
Tarantulas
Tarantulas
True Tarantulas are categorized as either New World or Old
World based solely on their geographic location.
Briesemeister Projection
Out with the Old in with the New
• New World Tarantulas appear to have a mild
temperament, thus seemingly they are more “tolerable”
of humans. It is thought that the behavior may be due to
an extra defense. Theses spiders have the ability to flick
urticating hairs off of their bodies, while Old World
Tarantulas can only envenomate presumed predators
(tarantulaguyuk, 2011).
– Urticating hairs of a tarantula will cause varying levels of
discomfort which include: burning, stinging, and itchiness. During
molting periods tarantulas may incorporate these hairs on the
webs as an additional deterrent to potential predators
(tarantulaguyuk, 2011).
Grammostola spatulata
http://aboutmonca.blog.cz/galerie/sklipkani/obrazek/6023307
Grammostola spatulata
• Geographic Location: Northern Chile and Argentina
(animal-world.com)
– G. spatulata is the brown variety of the Chilean Rose Hair
– New World Tarantula
• Lifespan of females is about 20 years and males live
about 6 years (animal-world.com)
• Typically very docile so they are commonly sold as low
maintenance pets
• Venom is nontoxic for humans (Dobson 2001)
GsMTx4
• Isolated from G. spatulata with a specificity
for particular mechanosensitive ion channels
(MSC). MSCs are ubiquitious non-specific
tissues.
• Target: Stretch activated MSCs
• Potential Treatment: for cardiac arrhythmia,
muscular dystrophy and glioma
GsMTx4 Mechanism
• The peptide binds to boundary lipids
surrounding the channel and alters the
voltage gated channel (Gottlieb et al. 2004)
– Boundary lipids are bent toward the channel
• Appears to be selective for Stretch Activated
Channels (Escoubas and Lachlan 2004)
http://www.nature.com/nature/journal/v4
30/n6996/images/nature02743-f1.2.jpg
GsMTx4 Mechanism
GsMTx4 alters the plasma membrane by bending
the areas around the stretch activated voltage
gated channels.
Poecilotheria regalis
http://www.mmo-champion.com
www.Beechhold,
Henry
Poecilotheria regalis
• pronounced pee-suh-luh-THI-ree-uh (Beechhold, 2000)
• P. regalis is known as the Indian Ornamental
– New World tarantula
• It is primarily arboreal (bighairyspiders.com)
• There haven’t been a lot of studies done on the venom of P.
regalis
– We decided to look up a couple of cases involving P. regalis
envenomation to see if we could come up with any ideas about
the potential type of venom it carries.
P. regalis venom
• Case 1
– "If you recall I mentioned that I was bitten by a 4 inch regalis last
week and reported no particular problems other than a sore finger,
of which the discomfort is slowly disappearing. I have now noticed
one or 4 other things. Now whether they are related to this bite I
simply don't know, only those who have been bitten before maybe
able to comment. 2 nights ago approximately 24 hours after the
bite my right calf muscle seized for approx. 5 minutes. I put this
down to a simple muscle cramp. (Had them before but not for a
few years). At approx. 6am in the morning I had another in the
same leg. Now this got me thinking if it was related to the T bite.
That day I seemed very tired, exhausted and wanted to sleep, but I
plodded on. The next day, still tired I finished work at 12pm dozed
on the sofa and at around 3pm I got the same cramp, only this time
in my left calf, later that day a muscle in my lower jaw temporarily
seized during a yawn.” (www.bighairyspiders.com)
P. regalis venom
• Case 2
– “In 2000, a middle-aged man was bitten on his finger by an
Indian Ornamental Tarantula (Poecilotheria regalis
Poecilotheriinae) whose body was 4 cm long. He developed local
swelling and erythema of the hand, and severe local pain. At
follow up, 8 days later, these symptoms had resolved but he still
had a tight feeling and cramps in the bitten hand and vague
generalized ‘flu-like’ myalgias (muscle pain). “ (Ahmed et al.
2009)
• Case 3
– A man bitten by Poecilotheria regalis “experienced violent pain
that radiated up the bitten arm into the axillary lymph nodes
and persisted for 20 min.” (Ahmed et al. 2009)
P. regalis venom
• Case 4
– Personal Blog with video here is the link if you want to check it out:
http://www.arachnoboards.com/ab/showthread.php?140875Poecilotheriaregalis&s=2ebd7a5f14e
6425f0d51a377fef376b1
“10:45pm - Initial bite:
Felt like a hot penny nail going through the skin. The actual bite felt hot - no little prick of pain,
just heat. I immediately took 4 Benedryl [sic]. My hand turned red in a matter of seconds and I
could actually feel the 'heat' going up my arm.
11:20pm:
Sweating profusely, cramps going all the way up my arm to my shoulder. Pain very bad!
12:20am:
Jaw started to hurt as well - other cramping continued. Pain about an 8 on a scale of 1-10. Left
to go to the ER to have my vitals checked. Heart rate was up but otherwise I was fine, except for
the cramping and pain. I was also nauseous by this point. Due to a 4 hour wait at the ER, I left at
this point.
12:40am:
Joints in my arms and legs started hurting really bad…shortness of breath continued. Benedryl
[sic] really kicking in now - very tired and dizzy. Walking was difficult due to being so dizzy, tired,
and having severe cramping.” (arachnoboards.com)
Venom Hypothesis
We believe that this venom is likely a neurotoxin
based on the localized pain and the muscle
cramps experienced by victims in all four cases.
There were additional cases of envenomation
that we read about, and muscle cramps continue
to be one of the major symptoms. Muscle cramps
may indicate that the venom has some effect on
potassium channels.
VENOMOUS SPIDERS COMMONLY
MISTAKEN FOR TARANTULAS
Phoneutria nigriventer
courtesy of João P. Burini
courtesy of João P. Burini
Phoneutria nigriventer
• “Phoneutria” translates to Murderess in Greek (Brazilian
Wandering Spider)
• Found throughout South America and Costa Rica (Brazilian
Wandering Spider)
• Commonly known as the Brazilian Wandering Spider or
Banana Spider
– This spider often hides in bunches of bananas during the day
• Can deliver potentially fatal doses of venom to humans
– LD50 = 200 µg/kg (Ori and Ikeda 1998)
PnTx2-6 Neurotoxin
• Isolated from P. nigriventer
• Target: calcium channels
• Potential Treatment: erectile dysfunction
(ED) (Nunes, 2010)
PnTx2-6 Mechanism for ED
• Pntx2-6 indirectly induces activity in
calcium channels which increases the
level of nitric oxide (NO).
• NO boosts circulation in the penis by
helping the walls of the blood vessels to
relax in cavernosal of rats (Nunes, 2010).
PnTx3-6
• PnTx3-6 was isolated from P. nigriventer
– potential safer alternative to morphine (addictive opiate)
and zinconotide which causes headache, nausea,
confusion, vomiting, etc. (De Souza 2011).
• Target: Ca2+ ion gated channels
• Potential treatment for allodynic, long-term, and
pre or postoperative pain
– Authors observed no neurological, cardiac, or
immunological side effects in any rats or mice. The
withdrawal symptoms were also less severe when using
PnTx3-6 (De Souza 2011).
PnTx3-6 Mechanism
• Molecular binding site is still unknown (Vieira
et al. 2005)
• Completely or incompletly blocks the external
pore of the calcium channels
• Complete blockage of N-type calcium channel
suggests that the toxin binds tightly to the
external mouth of the channel and physically
occludes the pore (Vieira et al. 2005).
Photo courtesy of Christian Bäckstam
Macrothele raveni
Macrothele raveni
• Commonly known as the Chinese Funnel
Web
• The body length of this hairy spider is
only 2-3cm (Zeng, et al 2003)
• The LD50 = 0.772 mg/kg of raventoxin-I in
mice (Zeng, et al 2003)
Macrothele raveni
• Venom isolated from M. raveni selectively
suppresses the growth of cancerous cells via
apoptosis
• Target: caspase 3 and caspase 8 pathways
• Potential Treatment: myelogenous leukemia
(Liu et al., 2012)
M. raveni venom
• Venom activates
caspase 3 an apoptosisrelated peptidase that
interacts with caspase
8.
– Caspase 3 plays a central
role in the executionphase of cell apoptosis
via the extrinsic signaling
pathway. (Clark and Tyler,
2009)
Clarke and Tyler, 2009
M. raveni venom
• In the extrinsic pathway,
death ligands bind and
activate their cognate
receptors (Fas). (Clarke
and Tyler, 2009)
• The toxin induces
apoptosis in
myelogenous leukemia
K562 cell line without
affecting other cells (Liu
et al., 2012)
Clarke and Tyler, 2009
Atrax robustus
http://www.arachnoboards.com/
Tirin/Ianmacm
Atrax robustus
• A. robustus is a venomous
funnel web spider centrally
located in Sydney, Australia
• One of the only spider species
with confirmed deaths
-Most appear to be caused by males
(inchem.org)
• The Sydney Funnel Web Spider
injects venom every time it
strikes
- This venom is known as Robustoxin
(inchem.org)
- LD50 = 0.16 mg/kg (Sheumack et
al. 1984)
http://www.micropest.com/
Robustoxin
• Robustoxin affects the cardiovascular system,
central nervous system and peripheral nervous
system
– Robustoxin alone causes a typical syndrome of
envenomation in primates and man of whole male
Atrax robustus venom. (Sheumack et al. 1984)
– On the autonomic system the venom causes both
inhibition of neurally mediated release of transmitters
(eg noradrenaline, acetylcholine) and an increase in
spontaneous transmitter release. A similar action on
the skeletal muscle neuromuscular junction has been
postulated (inchem.org)
Envenomation
Envenomation
• The bite causes intense pain and redness
• Symptoms of envenomation can be seen
within the first ten minutes.
– Symptoms include: muscle spasms, salivation or
lachrymation, piloerection (goose bumps),
tachycardia, shortness of breath, disorientation,
and confusion (inchem.org)
– Hypertension, hypotension, pulmonary edema,
and raised intracranial pressure can also occur in
severe envenomation (inchem.org)
Venom Optimization Hypothesis
The “venom
optimization hypothesis”
postulates that due to
the high metabolic costs
of venom regeneration,
venom dosage is
behaviorally controlled
and used as
economically as possible.
(Morgenstern & King,
2012)
Morgenstern and King, 2012
Antivenin
http://www.venompatrol.org
Focus
We focused specifically on antivenin for
the Sydney Funnel Web Spider (A.
robustus), because it has the most
confirmed fatalities out of all venomous
spiders. Antivenin isolated from the Sydney
Funnel Web Spider has also been used to
treat envenomation from another genera
of funnel web known as Hadronyche.
Background
• An antivenin from A. robustus
known as FWS AV went into use
beginning in 1980 (Graudins, et
al. 2002).
• Physicians began to treat bites
from Hadronyche genera with
FWS AV and noticed that
symptoms of envenomation
were alleviated in their
patients (Graudins, et al. 2002).
(Graudins, A., et al. 2002. )
• This map gives the location of
two genera of the Australian
Funnel Web Spiders (Atrax and
Hadronyche).
(Graudins, A., et al. 2002. )
The Research
Researchers confirmed that FWS AV can be used to treat envenomation
from both A. robustus and several species of Hadronyche spiders (H. versuta,
H. infensa, H. cerberea, and H. Formidabilis).
Antivenin Conclusion
• The ability to use the same antivenin across
multiple species of animals is known as
polyvalence.
• The polyvalence of FWS AV is likely due to
venom homologies across these two genera of
Funnel Web Spiders.
– Researchers believe it may be linked to
atracotoxins, which are shared by both genera.
(Graudins et al., 2002.)
Newly Discovered Species
Poecilotheria rajaei
Ranil Nanayakkara / British Tarantula Society
Poecilotheria rajaei
• pronounced pee-suh-luh-THI-ree-uh (Beechhold, 2000)
• Discovered and identified April 2013 in Sri Lanka
• Size of the human face
• Usually found in trees, however with habitat shrinking
found in old abandoned buildings (Drake, 2013)
• Not toxic to humans (Drake, 2013)
Summary
• Tarantulas and their close relatives both
produce venom that affect many systems of
the body. Their venom seems to be highly
specialized, and targets only particular ion
channels.
• Venom is constructed of numerous
compounds whose functions and
consequences vary based on environment.
Conclusion
• We realize that although we had a unnatural fear for
tarantulas and their sister taxa in the beginning , we
now respect them for the potential medical benefits
they can provide for us.
– Maybe that’s worth the creepiness of these wonderful
arachnids?
• Tarantula venom has novel compounds that come
with both positive and negative consequences.
Learning about these compounds may help to
develop new pharmaceuticals and new antivenins for
spider bites.
References
•
•
•
•
•
Ahmed, N., et al. 2009. “Symptom in search of a toxin: muscle spasms following
bites by Old World tarantula spiders (Lampropelma nigerrimum,Pterinochilus
murinus, Poecilotheria regalis) with review” Oxford University Press. Vol. 102
pp 851–857.
Beechhold, Henry F. "A Key to the Pronunciation and Meaning of Scientific Names
of Popular Species Part I: Pronunciation." A Key to the Pronunciation and
Meaning of Scientific Names of Popular Species Part I: Pronunciation.” The
American Tarantula Society, 2000. Web. 16 Apr. 2013.
<http://atshq.org/articles/beechwp1.html>.
"Brazilian Wandering Spider." Brazilian Wandering Spider. Turkcebilgi, 2010.
Web. 15 Apr. 2013. <http://english.turkcebilgi.com/Brazilian
wandering spider>.
Clarke, P. and Tyler, K.L. 2009. “Apoptosis in animal models of virusinduced disease” Nature Review Microbiology. Vol. 7 pp. 144-155
C., Rob. "P. Regalis Bite Report Thread: Poecilotheria Regalis." Web Blog post.
Arachnoboards RSS. vBulletin, Nov. 2007. Web. 17 Apr. 2013.
<http://www.arachnoboards.com/ab/showthread.php?140875
Poecilotheria-regalis>.
References
• De Souza, A.H., et al., 2011. “Antiallodynic effect and side effects of Phα1β,
a neurotoxin from the spider Phoneutria nigriventer: Comparison
with conotoxin MVIIA and morphine.” Toxicon Vol. 58 pp 626-633.
• Dobson, Roger, 2001. “Spider venom may prevent atrial fibrillation”
Western Journal of Medicine Vol. 3 pp 164.
• Drake, N., 2013 "New Giant Tarantula Discovered in Sri Lanka |
Wired.com." Wired Science. 2 Apr. 2013. Web. Date accessed
5 Apr. 2013.
• Escoubas, Pierre, and Lachlan, Rash. 2004. "Tarantulas: eight-legged
pharmacists and combinatorial chemists." Toxicon Vol. 43 pp. 555 –
574.
• Gottlieb, Philip A. et al. 2004. “Mechanosensitive Ion Channels as Drug
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• Graudins, A., et al., 2002. “Cross-reactivity of Sydney funnel-web spider
antivenom: neutralization of the in vitro toxicity of other
Australian funnel-web (Atrax and Hadronyche) spider venoms”
Toxicon Vol. 40 pp 259–266.
References
• Gurley, Russ, and Brough, Clarice. "Rose-haired Tarantula." Animal World.
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• Nunes, K.P, et al. 2010, “Nitric Oxide-Induced Vasorelaxation in
Response to PnTx2-6 Toxin from Phoneutria nigriventer Spider
in Rat Cavernosal Tissue” The Journal of Sexual Medicine
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References
• Schumm, Thomas. "Tarantula Bites!" Web log post. Phong's
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<http://www.bighairyspiders.com/bites.shtml>.
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