Study turns parasite invasion theory on its head

Dec 23, 2012
Toxoplasma gondii. Credit: AJ Cann

Current thinking on how the Toxoplasma gondii parasite invades its host is incorrect, according to a study published today in Nature Methods describing a new technique to knock out genes. The findings could have implications for other parasites from the same family, including malaria, and suggest that drugs that are currently being developed to block this invasion pathway may be unsuccessful.

Toxoplasma gondii is a parasite that commonly infects cats but is also carried by other warm-blooded animals, including humans. Up to a third of the UK population are chronically infected with the parasite. In most cases the causes only flu-like symptoms. However, women who become infected during pregnancy can pass the parasite to their which can result in serious health problems for the baby such as blindness and . People who have compromised immunity, such as individuals infected with HIV, are also at risk of serious complication due to reactivation of dormant found in the brain..

Researchers at the Wellcome Trust Centre for at the University of Glasgow made the discovery using a new technique to knock out specific genes in the parasite's genome. They specifically looked at three genes that are considered to be essential for the parasite to invade cells within its host to establish an infection.

"We found that we can remove each of these genes individually and the parasite can still penetrate the host cell, showing for the first time that they are not essential for host cell invasion as was previously thought," said Dr Markus Meissner, a Wellcome Trust Senior Research Fellow who led the study. "This means that the parasite must have other invasion strategies at its disposal that need to be investigated."

The genes the researchers looked at form the core of the parasite's gliding machinery that enable it to move around. In the past, researchers have only ever been able to reduce the of these genes in the parasite, which did lead to a reduction in host cell invasion but invasion was never blocked completely. This was attributed to the low levels of gene expression that persisted. However, with the new technique, the team were able to completely remove the genes of interest. Unexpectedly they found that the parasites were still able to invade.

"One of the we looked at is the equivalent of a malaria gene that is a major candidate for vaccine development. Our findings would suggest that such a vaccine may not be successful at preventing malaria infection and we need to revisit our understanding of how this family of parasites invades host cells," added Dr Meissner.

As well as malaria, a number of other parasites that affect livestock also belong to the same family. The findings could also provide clues to new treatments for these diseases, which cause substantial economic losses worldwide.

Explore further: How a molecular Superman protects the genome from damage

More information: N. Andenmatten et al. DiCre regulated, efficient genome engineering in Toxoplasma gondii uncovers an alternative invasion pathway. Nature Methods, 2012. [Epub ahead of print]

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Tausch
1 / 5 (5) Dec 23, 2012
"One of the genes we looked at is the equivalent of a malaria gene that is a major candidate for vaccine development. - Meissner


A setback. Alter mosquitoes' wingspan genetically for circular flight.
Ad nauseam stated until vaccine clinicals are completed.

Congratulations. A universal method for many parasitic infections.
RealScience
5 / 5 (1) Dec 23, 2012
@Tausch: And how would such an alteration spread among mosquitoes?
Tausch
1 / 5 (4) Dec 23, 2012
Mating.
The techniques for sterilization can be use to alter genes responsible for wing span.

If the alteration runs amok to all species, all species will be condemned to circular flight. The food chain remains intact.

Scientists from Imperial College London devised a way to inject mosquito embryos with a bit of RNA that disrupts one of the genes needed for sperm production, leading to healthy, but sterile, male mosquitoes.

Of course, there are lots of problems with using a system that could decimate an entire species–many other creatures, including our beloved bats, rely on mosquitoes for food, and so wide-scale eradication of mosquitoes isn't generally seen as a viable strategy. But the discovery could still be used to control mosquito population–and as malaria accounts for as many as 20% of childhood deaths in Africa, a controlled population could be invaluable.


http://www.united...-malaria
Tausch
1 / 5 (3) Dec 23, 2012
see above typo:
use=used
RealScience
5 / 5 (5) Dec 23, 2012
@Tausch: The alteration won't run amok. The circular flying mosquitoes will be at a huge disadvantage, and die out in a generation or two.

You'd have to go a step further to outsmart mother nature. You'd have to create an alteration that gives male mosquitoes, who don't bite people anyway, a >2x advantage in mating, and yet causes females to fly in circles.
2x advantages are hard to come by because nature would have already evolved them if it were easy. But maybe give the males the ability to digest some normally unavailable sugar (lactose?), and then put out trays of that sugar so that the males would be well fed and have nothing to do except mate.

But then why cause the females to fly in circles?
It would be easier to cause them to never hatch instead.
Tausch
1 / 5 (4) Dec 23, 2012
But then why cause the females to fly in circles?


The food chain remains intact. This species - male and female all fly circles.
The spread of malaria is local - regardless where the outbreak occurs.

The alteration won't run amok. The circular flying mosquitoes will be at a huge disadvantage, and die out in a generation or two.


You want the species that enables the transmission of malaria to die out - IF the alteration does not run amok - (crosses over to all other species). You want the outbreak of malaria localized for as long as the species remains living and flys circles.

You are deliberately confounding the solution. No idea why.
Anda
5 / 5 (2) Dec 23, 2012
What a nonsense, but keep on losing everybody's time, circular mind.
Tausch
1 / 5 (4) Dec 23, 2012
Obviously, one of your native languages is not English. This study exemplifies how time is lost.

You are being presumptuous to speak for everyone and their loss of time.
Tausch
1 / 5 (5) Dec 24, 2012
@Andra
Make a constructive comment that saves three thousand lives a day.
You have never saved even a single life have you?
Ojorf
4 / 5 (4) Dec 24, 2012
Tausch, almost any genetic adjustment you make to your mosquito will put it at a distinct disadvantage to the wild strain. Your alteration won't spread through the population since the very changes you are proposing lowers the insects fitness.
Tausch
1 / 5 (2) Dec 24, 2012
Be more specific. What aspect of circular flight lowers the insects' fitness? The radius of flight? Or is survival fitness what you are addressing.
C_elegans
5 / 5 (2) Dec 24, 2012
Tausch, you have no clue. Try starting with Darwin's The Origin of Species before you lambast others while claiming you save thousands of lives by playing armchair quarterback. Your breeding males will be quickly selected against and removed from the breeding population. The females that they mate will never find food for reproduction, whereas wild-type mosquitoes that do find a blood meal continue to propagate.

This study emphasizes that we cannot half-ass science. To know a gene's function - knock it out not down.
Tausch
1 / 5 (3) Dec 25, 2012
So the work done up until now is half-ass?
You 20/20 hindsight is guiding you, not science.
Be specific. What factors contribute against selection.

State or quote where I claim I save thousands of lives -
by playing armchair quarterback.
Drop your aggression.
C_elegans
not rated yet Dec 25, 2012
Mosquitos that fly in circles cannot find adequate food, therefor they die and do NOT have offspring. This is biology 101, where you can learn about the selection of white rabbits in snow-covered climates.

Additionally, the article is truly meant to promote their new gene-deletion technique, whereas past methods used RNAi. Not that you would understand the difference, or even the point of this study.

Finally, Merry Christmas, Tausch.

@Andra
Make a constructive comment that saves three thousand lives a day.
You have never saved even a single life have you?

Tausch
1 / 5 (1) Dec 25, 2012
To -c_elegans and to all:
The promise that progress provides begins with every new and passing year.
Tausch
1 / 5 (2) Dec 27, 2012
[Not that you would understand the difference, or even the point of this study. - C_
In both cases - RNAi and 'gene-deletion technique' - I understand the difference as well as the point of this present study.
Labeling the applied past methods of RNAi as 'half-assed' science is beyond me:
This study emphasizes that we cannot [do] half-ass science.-C_

Maybe this is your sense of frustration in light of the daily lives lost.

Your extension of "white rabbits in snow-covered climates and biology 101" extrapolating to mosquitoes is beyond me as well.

Mosquitoes that fly in circles are subjected to wind drift. They are still localized. You say starvation can be the only outcome.
I said this 'quick fix' is worth a try until the study above bears a vaccine that targets those genes leading to eradication. Especially in light of the time and money already expended.

Called the suggestion half baked. That is your prerogative.

RealScience
5 / 5 (1) Dec 27, 2012
@Tausch - please try the experiment you propose and write up the results. If it is as easy to do as you imply, and works as well as you think, you'll save millions of lives.

In the mean time please refrain from criticizing the efforts of others who try experiments to test their own theories.
Tausch
1 / 5 (1) Dec 27, 2012
@RealScience
Where did I criticized the efforts of others who try experiments to test their own theories? Simply quote the passage I stated.

I congratulated the efforts put forth so far. See first post.

The 'quick fix' does not imply 'easy' as you infer.
It implies this can be implemented faster and cheaper because the need for clinical trials and distribution are absent until such a vaccine is available.
RealScience
5 / 5 (2) Dec 27, 2012
@Tausch - I took referring to your idea as a quick fix and your comment
... until the study above bears a vaccine that targets those genes leading to eradication. Especially in light of the time and money already expended.


to be a criticism of that work as not as practical as your idea.
And I took the 'universal method' in your first comment to be a reference to your proposal, not the proposal in the article.

If your comment was not meant as criticism, and your congratulations were for the work on the article was based, then I do apologize for having misinterpreted your remarks.
Tausch
1 / 5 (1) Dec 27, 2012
Accepted.
The strategy to develop a vaccine is the best strategy. A suggestion such as mine is a 'patch' - to use computer jargon - until a vaccine program has been implemented and established.

To repeat - the new technique has enable this team to completely remove the genes of interest and brings any vaccination program that much closer and faster to the success all researchers are seeking.
Tausch
1 / 5 (1) Dec 28, 2012
@RealScience
You often misinterpret and misunderstand comments put forth on this science news website.

The authors' proposal suggested to apply the newly discovered technique to establish which genes are responsible for the pathogen's ability to invade a host cell.

There is nothing new or 'universal' about my method of proposal.
It is tailored to the malaria-carrying species in question.

To come to a science news website and congratulate myself for any idea that temporarily mitigates a dire situation makes no sense.

Misconstruing others' statements imparts a confrontational impression upon those participating in commentary.

Without exception the articles reporting research here are incomplete.
Which is why serious commentators read the original research first - before commenting.

Without exception you will experience hostile readers.
Numberless comments such as:
"You have no clue"

hallmarks all confrontational nonconstructive readers.
RealScience
5 / 5 (2) Dec 28, 2012
@Tausch:
I agree completely with you that hostile readers should keep aggressive thoughts to themselves rather than posting them as comments. Civil discourse is far more productive than flame wars.

I did find the comment that caused me to interpret your comments as critical of the study:
This study exemplifies how time is lost.

This sounded like "the study was a waste of time", but with your recent explanation I understand see that you were saying "due to setbacks time was lost in the battle against malaria".

I try to read the article and the comments carefully before commenting, and to give the benefit of the doubt until people remove all doubt, but I can see that in this example I was not careful enough. Can you give additional examples of where I have misinterpreted so that I can learn?
Tausch
3 / 5 (2) Dec 28, 2012
We have cleared up all misapprehensions between us on this commentary thread.
You have pointed out where statements I made are open to interpretation.

There are no more examples stemming from our mutual dialogues that are open to interpretation. That was our mutual learning.

Thank you for pointing out the less-than-clear statement:
This study exemplifies how time is lost.


with
Due to setbacks time was lost in the battle against malaria


A statement not open to interpretation or further improvement. Well done. Of course hostile readers will read whatever they want to read into words and in between the lines.


Tausch
3 / 5 (2) Dec 28, 2012
...but with your recent explanation I understand [and?] see that you were saying...

Is the word 'and' missing in your original sentence?

Are the words 'are' and 'of' missing in my original sentence?

...[are] hallmarks [of] all confrontational nonconstructive readers.

Everyone is prone to harmless errors as well.
RealScience
5 / 5 (2) Dec 28, 2012
I read my comments before posting, and about half the time I still find an error and use the edit button right after I submit. And even then about half the time I see an error when I re-read one of my comments later after someone comments on a comment.

Missing short connecting words like 'and' and 'of' is the most common error, and is generally harmless. But I've even found places where I've missed a 'not', which is much more serious.

After catching plenty of errors in my own careful writing, I've learned to appreciate just how easy errors are and how smart our genomes are to have learned not only to fix most errors and to tolerate most of the unfixed errors, but to even use the remaining errors to drive evolution forward.