Stem Cells in Schistosomes!

Good news everyone! A parasite-related paper was released on Wednesday in Nature that involved those monogamous little blood flukes we call the schistosomes! The paper was titled "Adult somatic stem cells in the human parasite Schistosoma mansoni" and it brought up some interesting new information regarding how these worms live so long.

These worms are well-known for their longevity. S. mansoni has been known to live for years, even decades within their hosts.  These worms live an average of 5-6 years, however there are reports of people becoming infected during childhood and not developing clinical symptoms until adolescence or adulthood. 

A composite image of a scanning electron micrograph
of a pair of male and female Schistosoma mansoni with
the outer tegument (skin) of the male worm "peeled back" (digitally)
to reveal the stem cells (orange) underneath. (Credit: Jim Collins,
Ana Vieira and Phillip Newmark, Howard Hughes Medical Institute
and University of Illinois at Urbana-Champaign)

This newly released study reveals that these worms may be able to achieve such long live spans through the use of stem cells. These findings aren't completely shocking.  These flukes are related to a type of non-parasitic flatworm known as Planaria.  These adorable little turbellarians are often used in zoology labs to demonstrate regeneration to students.  They have a remarkable ability to regenerate from longitutinal and transverse cuts because they house special stem cells known as neoblasts. Stem cells, by definition are able to develop into any type of cell the worm needs...blood cells, muscle cells, etc.  Neoblasts don't just help the Planaria regenerate damaged tissues, they also help to repair tissues that become damaged over time as the worm ages.

Lead researcher Phillip Newmark wondered if maybe schistosomes were living so long because they also had stem cells that repaired damaged tissues to keep the worms young. Following up on his suspicions, he and his team began searching for these cells in schistosomes.

They used fluorescent tagging techniques to find actively dividing cells within the blood flukes, then they isolated the cells and studied them.  Through their observations of these cells, they were able to determine that the cells divided to create two new cells: one that differentiated into another cell type (which varied) and one that was another stem cell.  This is characteristic about what is already known of stem cells.

Here's a quote from Newmark about the research:

The cells we found in the schistosome look remarkably like planarian neoblasts. They aren’t associated with any one organ, but can give rise to multiple cell types. People often wonder why we study the ‘lowly’ planarian, but this work provides an example of how basic biology can lead you, in unanticipated and exciting ways, to findings that are directly relevant to important public health problems.

 
This paper isn't insinuating that these neoblast-like stem cells are the only reason that schistosomes can live for so long, it is merely demonstrating that having these cells plays a role in their longevity. With continued research, it is believed that new treatments for curing people of schistosome infections will be created that target these stem cells for more efficient killing of the parasite.

Isn't biology fascinating?! There's always something new to learn about things that we have spent decades and probably millions...maybe even billions...of dollars researching! Yay for a field that is ever-changing and oh-so-exciting! :D

Zombie-Slave Spiders

I love spiders.  I'm also a big fan of zombie-lore, and of course of parasites.  This week, I decided to bring those three things together to tell you about a species of parasitic wasp that infects spiders.  This parasitic wasp (belonging to the genus Zatypota) hijacks the spider's body making it not only a zombie, but also a slave.  Infected spiders spin slightly abnormal webs to make better areas for the parasites' cocoons.

Zatypota specimen
mounted on a pin.

There are probably hundreds of species of parasitic wasps.  Most of theses belong in the family Ichneumonidae.  (In fact, they might all be in this family...but I can't remember, and I don't want to lie to you!) Within this family is a subgrouping that includes wasps that specifically parasitize spiders.  Members of this group are known as polysphinctine wasps. The female parasitic wasps use their ovipositors to insert eggs into the bodies of many different types of hosts...caterpillars, cockroaches, and as you will soon learn, spiders.  These wasps' eggs usually hatch within the host, using it as a food source, shelter, and in some cases as a vehicle to a more suitable emergence area.  Today, we will look specifically at a type of parasitic wasp that infects a spider that lives in the rainforests of Costa Rica.

Anelosimus octavius is a type of spider belonging in the trash-web family, Theridiidae.  This family is full of spiders with large abdomens that are carried in a distinctive way by members of this family.  I can't describe this very well...it's really something you just have to see to understand.  This family is also known as the family of  "comb-footed" spiders due to these neat little modifications they have on their back set of legs. Spiders in this family are also sometimes referred to as "cobweb" spiders because their webs take on a haphazard cotton-y appearance rather than the intricate patterns created by orbweavers or the distinctive sheets made by funnel-web spiders and their relatives.  Some of the more infamous members of this family include members of the genus Laterodectus...also known as black widows.

A typical web built by Anelosimus octavius.

Getting back to our little Zatypota, this wasp, like other polysphinctine wasps, modifies the behavior of their spiders hosts.  More specifically, these parasites modify the spiders' web-building behaviors. After a female wasp inserts its eggs into the spider hosts, the wasp larvae grow for about a week, feeding on the spiders' hemolymph for sustenance. Then, the larvae commands the spider to construct a modified "cocoon web".  Then the larvae emerge from their hosts, eat the hosts, then build a cocoon next to the cocoon web in which to pupate.  The idea is that these cocoon webs and other parts of modified web structures increases the likelihood of survival for the wasps by serving as additional protection during the pupal stage.

Central platform of web
showing top of wasp cocoon.

According to reports of observations of infected spiders, the hosts spend a great deal of time and effort preparing the cocoon webs for their parasites.  After tireless efforts, the exhausted spiders crawl back into the central part of the site only to become immobile  before being consumed by its parasite.  The following day, the parasite would began constructing its own cocoon right on top of the area where it ate its host.

It is interesting to think about how this could have evolved among these two species! However it happened, this is yet another awesome example of behavioral modification due to parasitism.  Hooray for making your hosts into zombies!

This is from a paper describing the odd behavioral changes induced by these parasitic wasps.
"Figure 2: Cocoon web of A. nr. studiosus (a) in which the wasp larva holds onto the densely-meshed central area just after having discarded the corpse of the spider. Lateral (b) and dorsal (c) views of wasp cocoons in cocoon webs of A. octavius, showing the radial pattern of lines around the upper end of the cocoon (c), and that the lines intersecting the cocoon (indicated by small “pimples”) are in the upper portion of the cocoon, with an open space below in which the cocoon hangs free (bar in (b)). The cocoon web spun from scratch in captivity (d) incorporated flat leaves (covered with white dust in the photo) as parts of the sheet."

Toxo on the Brain

Toxoplasma gondii is one of those parasites that, once you learn about what it's capable of, you can't get it out of your head.  In some cases, that could be taken literally.  To learn the basics about this parasite, see this previous post.  Did you read it? Good! Let's move on.

Since the early 90's, scientists have known that T. gondii causes drastic behavioral changes in rats and mice.  It represses the animals' innate fears by essentially screwing with their brain chemistry until they start to actually like the odor of cat urine rather than being afraid of the scent.  This behavioral change is believed to be instigated by the parasite in order to get it into the definitive host (a cat).

Those studies were vastly interesting, but in recent years scientists have begun to find correlations between  toxoplasmosis and changes in human behavior.  Therefore, we will focus on the research presented with regard to human manipulation as opposed to rodent manipulations for the purposes of this post.

The idea that Toxoplasma could actually affect human behavior was radical when first proposed by a Czech biologist named Jaroslav Flegr.  His work has been highly controversial among people within the scientific community, but his diligence has paid off.  In November of 2012, a group of Swedish researchers discovered that this parasite hijacks white blood cells in order to make its way to the brain. Back in 2009, U.K. scientists discovered that this parasite has two genes for making a precursor molecule for the production of dopamine (1-DOPA, in case you were wondering). Upon further testing, it was found that the parasite induces the upregulation of dopamine production once in the brain of rats, and later it was found that infected humans also have increased levels of this neurotransmitter.

A Pseudocyst of parasites that forms in the brain.

The significance of increased dopamine production is how dopamine affects our behaviors. It was noted in rats to affect male and female rats differently, something that is, again, reflected in infected humans. In men, the increase in dopamine leads to a decrease in the production of the stress-hormone known as cortisol. This causes a spike in testosterone levels, which can drastically change a man's personality. These changes include increased aggression, social difficulties, increased dominance, impulsiveness, and a disinterest in the feelings of others (often to the point of psychopathy).

The increased production of dopamine in females causes very different changes.  Women's bodies are more adapted to dealing with increases in dopamine levels.  To cope with this, a female's body releases an influx of the sex hormones oestrogen and progesterone into the dopamenergic systems.  Unlike in men, this causes an increase in cortisol production in females, which drops the already low levels of testosterone.  Infected women tend to be less impulsive, more sensitive to the needs of others, more motivated, more outgoing, and more relaxed.  However, they do seem to experience hair loss and lowered libido in response to infection.

The personality changes described above become more drastic over time. Regardless of gender, infected people have been shown by some of Flegr's studies to be almost twice as likely to be involved in a car accident.  This is because the parasite leads humans to having slower reaction times and increased fatigue.  Infected people have an increased risk of both suicide and of developing mental problems for which they will need to be institutionalized for their own safety.  There are also many links between toxoplasmosis and psycological disorders. Mood disorders such as bipolar disorder and clinical depression have been connected  with infection as has obsessive-compulsive disorder.

The disorder that has been most studied in connection with toxoplasmosis is schizophrenia.  Dopamine plays a big role in the development of schizophrenia.  Many people diagnosed with this disorder test positive for Toxoplasma gondii antibodies.  The link between schizophrenia and toxoplasmosis is still being studied, but it makes sense that an interplay could be present due to their connections with dopamine.

Toxoplasma gondii in green,
multipling inside a dendritic cell.

I mentioned earlier, it was recently discovered that the parasites hitch rides on white blood cells.  To be more specific, they grab hold of dendritic cells and use them to get into the host's brain. To get the dendritic cells to move, the parasites induce these cells to produce GABA (a neurotransmitter).  Like igniting a flame, the release of GABA by the dendritic cells excites GABA receptors outside the cell and sends it blasting through the body until it reaches the brain.  Another interesting thing about GABA? Changes in GABA levels are associated with psychiatric disorders such as...you guessed it...schizophrenia.

Now let's switch gears...we know that this tiny, single-celled protist may be the cause of some serious neurological disorders and that it induces some interesting changes in personality.  But this parasite isn't all bad, it has been reported that women infected with an asymptomatic form of toxoplasmosis (known as "latent toxoplasmosis") may benefit from the infection.  It seems that women infected with this prior to pregnancy are protected from contracting acute toxoplasmosis and their fetuses are protected from getting congenital toxoplasmosis! How cool is that?

It gets cooler!  Some scientists are doing cutting-edge research on using this parasite to TREAT neurological problems.  Yes, you read that right!  It seems that controlled infections can help people with problems relating to decreases in dopamine, such as ADD and ADHD.  It is also being used in researching treatments for both Parkinson's disease and Alzheimer's disease!

I guess that just goes to show you that there are two sides to every coin...or in this case, to every unicellular eukaryotic endoparasite! :p  With all of the advances being made in helminthic therapy, it will be great to see what medical science is able to do to utilize the manipulative capabilities of this parasite in the treatment of low-dopamine related disorders.

Who can resist posting rainbow pictures of parasites?!

New Insights on Old Worms

As we've seen with past work, it's not easy to find parasites in coprolites that date back to 270 million years ago.  However, a team of researchers has found such diamonds in the rough...if you think of tapeworm eggs as tiny diamonds, and fossilized shark poop as the rough.

Shark coprolite containing 270 million year old tapeworm eggs.

These researchers published their work in PLoS One in January of this year (2013). From a Brazilian coprolite dating back to the Paleozoic era, this team found a group of 93 tapeworm eggs.  Like modern fish tapeworm eggs, these possessed a single operculum, and one even looked to contain a developing larva.  The oval-shaped eggs were beautifully preserved inside the coprolite encased within what appears to have been a proglottid. 

#1, this is awesome because it is the first time that tapeworm eggs have been recovered from anything that is this old.  We are talking older by FAR...these eggs predate parasites found in the fossil record dating back to dinosaurs. In fact, these eggs predate known instances of any form of vertebrate parasites by about 140 million years.  This sets the evolutionary time stamp much further back for intestinal parasites than we ever thought they had existed. (This is why biology is awesome! What we think we know today, could be completely wrong with the discoveries of tomorrow!)

This discovery will hopefully spur the interest of other researchers into doing paleoparasitology work.  It is absolutely amazing to have the definitive proof of the existence of something as soft-bodied as a tapeworm preserved for 270 million years.  This discovery was made from just one of over 500 similar coprolites located in a single area where researchers believe fish may have been trapped due to a dry spell.

270-million-year-old tapeworm eggs from a section taken from a shark coprolite.  In "A" you can see the proglottid surrounding the eggs.  In "B" you can see the eggs up close...the arrows indicate the opercula.

The state of preservation was astounding.  There was quiet a bit of pyrite (fool's gold) found in the coprolites, which tells us that the environment must have been pretty well depleted of oxygen.  Even though these coprolites can tell us a lot about the environmental conditions at the time of deposition, the exact species that deposited the coprolite will remain a mystery since all shark poop looks the same.

The tapeworm species is yet to be determined, but is similar to extant species found within Tetraphyllidea (which contains 540 extant species that parasitize Elasmobranchs).

I can't wait to see just how much more we discover about these little dudes in the coming year! :)