Fwd: [health-vn] Giardia : Coat of Many Proteins May Be This Parasite’s Downfall - GMS Professional Network on Parasitic Diseases

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Date: Wed, 17 Dec 2008 09:51:56 +0700
From: "Stephane P. ROUSSEAU" <gms.cdc...@gmail.com>
To: gms-professional-network-on-parasitic-diseases@googlegroups.com
Subject: =?WINDOWS-1252?Q?Fwd:_[health-vn]_Giardia_:_Coat_of_Many_?= =?WINDOWS-1252?Q?Proteins_May_Be_This_Parasite=92s_Downfall?=
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FYI.
Comments and exchanges are most welcome.
Note: by sending emails to
gms-professional-network-on-parasitic-diseases@googlegroups.com you'll be
addressing at once all professionals who have expressed interest in
parasitic diseases in the GMS CDC Directory, without the risk of your email=
s
being caught by spammers. Do not hesitate to share then !

Kind regards
Stephane


---------- Forwarded message ----------
From: Vern Weitzel <vern.weit...@gmail.com>
Date: Wed, Dec 17, 2008 at 1:53 AM
Subject: [health-vn] Giardia : Coat of Many Proteins May Be This Parasite's
Downfall
To: "[health-vn discussion group]" <health...@cairo.anu.edu.au>


sent to health-vn MDG List by Vern Weitzel <vern.weit...@gmail.com>

http://www.nytimes.com/2008/12/16/science/16giar.html?_r=3D1&ref=3Dscience

Coat of Many Proteins May Be This Parasite's Downfall

By NICHOLAS WADE
Published: December 15, 2008
If you return from a trip abroad to find you have projectile vomiting,
roaring flatulence, sulfurous belching and explosive diarrhea, the bad news
is that you won't die; you just have an attack of giardiasis, a form of
purgatory devised by the single-celled parasite known as giardia.

Enlarge This Image

P. M. Motta and F. M. Magliocca/Photo Researchers
SHIFTY When giardia must wear all its 190 coat proteins at once instead of
selecting one and changing it often, it cannot hide from the immune system.
Related
Health Guide: Giardiasis

RSS Feed
Get Science News From The New York Times =BB
Giardia infections can linger for months because the parasite plays a
cunning defense against the body's immune system. In its genomic wardrobe,
it has 190 coats to choose from. As soon as the immune system has generated
antibodies against one coat, giardia switches to another. Because of the
parasite's persistence and infectivity, some 280 million cases of giardiasi=
s
occur in the world each year, the World Health Organization estimates,
though most of these are in developing countries where people are more
inured to the disease.

Giardia's offensive game could have a fatal weakness, however. Biologists
led by Hugo D. Luj=E1n at the Catholic University of C=F3rdoba in Argentina=
 have
gained a striking insight into its coat-shuffling stratagem.

With this knowledge, they have accomplished a cunning counterploy: they hav=
e
forced the parasite to make and wear all its coat proteins at the same time=
.
This altered parasite, they hope, should serve as the perfect vaccine,
because it immunizes the body to the full repertoire of giardia's coat
proteins all at once. The idea has worked well in animal tests, Dr. Luj=E1n
said.

He thinks the same general approach =97 forcing expression of all coat
proteins simultaneously =97 might help produce vaccines against the other
protozoan parasites that rely on coat switching to dodge the immune system.
These include malaria and the trypanosomes that cause sleeping sickness and
Leishmaniasis.

Dr. Luj=E1n and his team have identified the mechanism by which giardia
controls its coat proteins, they report in the current issue of Nature. Eac=
h
of the parasite's 190 coat genes is the recipe for making a different
protein, and the parasite switches its coat every 10 generations or so. To
produce the coat, giardia does not switch these genes on one at a time, as
might be expected. Instead, it seems to leave them all turned on, allowing
each to generate a messenger RNA copy of itself. Usually the messenger RNAs
would direct the synthesis of proteins, but giardia then destroys all but
one of the messengers, and the survivor makes the coat of the day.

To kill its messenger RNAs, giardia has adapted an ancient cellular system
known as RNA interference. The system is designed to destroy foreign RNA,
like that of invading viruses, so it was surprising to find it regulating a
cell's own RNAs, Dr. Luj=E1n said.

He proved this was the case by disrupting giardia's production of enzymes,
like those known as Dicer and Argonaute, that are components of the RNA
interference system. With its RNA selection system out of business, giardia
produces many =97 Dr. Luj=E1n believes probably all =97 of the coat protein=
s in
its repertoire and inserts them into its outer covering.

He said he did not yet know how the organism shifted between coats but
suspected that the RNA interference system favored whichever messenger RNA
happened to be the most abundant at the time, and destroyed all others.

In an experiment that has not yet been published, Dr. Luj=E1n has tested
gerbils, the laboratory animal often used in giardia work, with a vaccine
consisting just of giardia with its RNA interference system blocked. "We sa=
w
complete protection," he said.

Dr. Theodore E. Nash, a leading expert on giardia at the National Institute=
s
of Health, said the new report was "a major advance in the field." Since
1979, Dr. Nash has developed many of the methods to study giardia and its
coat shuffling, several of which were used by Dr. Luj=E1n, who worked for f=
ive
years in Dr. Nash's lab.

Another giardia expert, Dr. Rodney Adam of the University of Arizona, said
Dr. Luj=E1n's work on giardia's coat gene control was interesting "but not =
the
whole story." As for making a vaccine, he said that "this is not an organis=
m
to which natural infection will confer immunity." People in developing
countries may get one infection after another, although they do get a much
less severe form of the disease.

Malaria also evades the immune system by switching its protein coat. Dr.
Kirk Deitsch, an expert on malaria coat genes at the Weill Cornell Medical
College, said Dr. Luj=E1n's new finding "may be conceptually applicable to
malaria," although the malaria parasite does not use RNA interference and n=
o
one yet knows how to make it display all its 60 coat protein genes at once.

A human vaccine for giardia could be of great benefit if the many mild case=
s
in the developing world do in fact undermine health. Some experts believe
persistent giardia infection causes malnutrition, but others are less sure
of this.

For the much smaller number of Westerners who are not inured to the disease=
,
a vaccine would be a welcome addition to the few available drugs. It would
have been a godsend for the Crusaders, who are known from historical
accounts to have suffered terribly from a variety of intestinal diseases
that had no respect for rank. In 1249 King Louis IX, who led the Seventh
Crusade, had such serious diarrhea that part of the monarch's breeches were
cut away to ease his personal hygiene. Giardia may well have been his
tormentor. Using a sensitive immunological test, researchers who excavated =
a
medieval latrine in the city of Acre, once part of the Crusader kingdom of
Jerusalem, detected the presence of giardia, they reported in the July issu=
e
of The Journal of Archaeological Science.

Giardia itself is far more ancient than any Crusader kingdom. Though a
single-celled organism, it belongs to the eukaryotes, the domain that
includes all plants and animals. In the tree of eukaryotic life, giardia
belongs to one of the earliest branches. It lacks mitochondria, the
energy-producing organelles that are almost a badge of eukaryote identity.
Even stranger, each giardia cell possesses two nuclei; no one knows what
benefit offsets the cost of maintaining the second. Before this enigmatic
microbe plagued people, it was doubtless the scourge of many earlier
species. Dr. Luj=E1n's discovery may be a critical step in curbing giardia'=
s
merciless torment of its fellow eukaryotes.

health-vn List
Bringing Millennium Development Goals Closer to the People
email the list: <health...@cairo.anu.edu.au>
To subscribe/unsubscribe contact: Vern Weitzel <v...@coombs.anu.edu.au>
Other lists: http://coombs.anu.edu.au/~vern/forum.html<http://coombs.anu.ed=
u.au/%7Evern/forum.html>

The accuracy of information from media articles posted on this list
cannot be guaranteed and should be verified before use. Your
comments to the list on these stories are most welcome!



--=20
_______________________
St=E9phane P. Rousseau (Mr)
Regional Coordinator

Regional Coordination Unit (RCU)
Asian Development Bank
Greater Mekong Communicable Diseases Control Project
Room 2104, 21st Floor,
Thanh Cong Tower,
57 Lang Ha Street,
Ba Dinh District, Hanoi =96 VIET NAM

Tel: +84 (0) 43 514 79 33
Fax: +84 (0) 43 514 80 12
Email: gms.cdc...@gmail.com
Website: http://gms-cdc.org/index.php

------=_Part_84612_9403255.1229482316155
Content-Type: text/html; charset=WINDOWS-1252
Content-Transfer-Encoding: quoted-printable
Content-Disposition: inline

FYI. <br>Comments and exchanges are most welcome. <br>Note: by sending emai=
ls to <a href=3D"mailto:gms-professional-network-on-parasitic-diseases@goog=
legroups.com">gms-professional-network-on-parasitic-disea...@googlegroups.c=
om</a> you&#39;ll be addressing at once all professionals who have expresse=
d interest in parasitic diseases in the GMS CDC Directory, without the risk=
 of your emails being caught by spammers. Do not hesitate to share then !&n=
bsp; <br>
<br>Kind regards<br>Stephane<br><br><br><div class=3D"gmail_quote">--------=
-- Forwarded message ----------<br>From: <b class=3D"gmail_sendername">Vern=
 Weitzel</b> <span dir=3D"ltr">&lt;<a href=3D"mailto:vern.weit...@gmail.com=
">vern.weit...@gmail.com</a>&gt;</span><br>
Date: Wed, Dec 17, 2008 at 1:53 AM<br>Subject: [health-vn] Giardia : Coat o=
f Many Proteins May Be This Parasite's Downfall<br>To: &quot;[health-vn dis=
cussion group]&quot; &lt;<a href=3D"mailto:health...@cairo.anu.edu.au">heal=
th...@cairo.anu.edu.au</a>&gt;<br>
<br><br>sent to health-vn MDG List by Vern Weitzel &lt;<a href=3D"mailto:ve=
rn.weit...@gmail.com" target=3D"_blank">vern.weit...@gmail.com</a>&gt;<br>
<br>
<a href=3D"http://www.nytimes.com/2008/12/16/science/16giar.html?_r=3D1&amp=
;ref=3Dscience" target=3D"_blank">http://www.nytimes.com/2008/12/16/science=
/16giar.html?_r=3D1&amp;ref=3Dscience</a><br>
<br>
Coat of Many Proteins May Be This Parasite's Downfall<br>
<br>
By NICHOLAS WADE<br>
Published: December 15, 2008<br>
If you return from a trip abroad to find you have projectile vomiting, roar=
ing flatulence, sulfurous belching and explosive diarrhea, the bad news is =
that you won't die; you just have an attack of giardiasis, a form of purgat=
ory devised by the single-celled parasite known as giardia.<br>

<br>
Enlarge This Image<br>
<br>
P. M. Motta and F. M. Magliocca/Photo Researchers<br>
SHIFTY When giardia must wear all its 190 coat proteins at once instead of =
selecting one and changing it often, it cannot hide from the immune system.=
<br>
Related<br>
Health Guide: Giardiasis<br>
<br>
RSS Feed<br>
Get Science News From The New York Times =BB<br>
Giardia infections can linger for months because the parasite plays a cunni=
ng defense against the body's immune system. In its genomic wardrobe, it ha=
s 190 coats to choose from. As soon as the immune system has generated anti=
bodies against one coat, giardia switches to another. Because of the parasi=
te's persistence and infectivity, some 280 million cases of giardiasis occu=
r in the world each year, the World Health Organization estimates, though m=
ost of these are in developing countries where people are more inured to th=
e disease.<br>

<br>
Giardia's offensive game could have a fatal weakness, however. Biologists l=
ed by Hugo D. Luj=E1n at the Catholic University of C=F3rdoba in Argentina =
have gained a striking insight into its coat-shuffling stratagem.<br>
<br>
With this knowledge, they have accomplished a cunning counterploy: they hav=
e forced the parasite to make and wear all its coat proteins at the same ti=
me. This altered parasite, they hope, should serve as the perfect vaccine, =
because it immunizes the body to the full repertoire of giardia's coat prot=
eins all at once. The idea has worked well in animal tests, Dr. Luj=E1n sai=
d.<br>

<br>
He thinks the same general approach =97 forcing expression of all coat prot=
eins simultaneously =97 might help produce vaccines against the other proto=
zoan parasites that rely on coat switching to dodge the immune system. Thes=
e include malaria and the trypanosomes that cause sleeping sickness and Lei=
shmaniasis.<br>

<br>
Dr. Luj=E1n and his team have identified the mechanism by which giardia con=
trols its coat proteins, they report in the current issue of Nature. Each o=
f the parasite's 190 coat genes is the recipe for making a different protei=
n, and the parasite switches its coat every 10 generations or so. To produc=
e the coat, giardia does not switch these genes on one at a time, as might =
be expected. Instead, it seems to leave them all turned on, allowing each t=
o generate a messenger RNA copy of itself. Usually the messenger RNAs would=
 direct the synthesis of proteins, but giardia then destroys all but one of=
 the messengers, and the survivor makes the coat of the day.<br>

<br>
To kill its messenger RNAs, giardia has adapted an ancient cellular system =
known as RNA interference. The system is designed to destroy foreign RNA, l=
ike that of invading viruses, so it was surprising to find it regulating a =
cell's own RNAs, Dr. Luj=E1n said.<br>

<br>
He proved this was the case by disrupting giardia's production of enzymes, =
like those known as Dicer and Argonaute, that are components of the RNA int=
erference system. With its RNA selection system out of business, giardia pr=
oduces many =97 Dr. Luj=E1n believes probably all =97 of the coat proteins =
in its repertoire and inserts them into its outer covering.<br>

<br>
He said he did not yet know how the organism shifted between coats but susp=
ected that the RNA interference system favored whichever messenger RNA happ=
ened to be the most abundant at the time, and destroyed all others.<br>

<br>
In an experiment that has not yet been published, Dr. Luj=E1n has tested ge=
rbils, the laboratory animal often used in giardia work, with a vaccine con=
sisting just of giardia with its RNA interference system blocked. "We saw c=
omplete protection," he said.<br>

<br>
Dr. Theodore E. Nash, a leading expert on giardia at the National Institute=
s of Health, said the new report was "a major advance in the field." Since =
1979, Dr. Nash has developed many of the methods to study giardia and its c=
oat shuffling, several of which were used by Dr. Luj=E1n, who worked for fi=
ve years in Dr. Nash's lab.<br>

<br>
Another giardia expert, Dr. Rodney Adam of the University of Arizona, said =
Dr. Luj=E1n's work on giardia's coat gene control was interesting "but not =
the whole story." As for making a vaccine, he said that "this is not an org=
anism to which natural infection will confer immunity." People in developin=
g countries may get one infection after another, although they do get a muc=
h less severe form of the disease.<br>

<br>
Malaria also evades the immune system by switching its protein coat. Dr. Ki=
rk Deitsch, an expert on malaria coat genes at the Weill Cornell Medical Co=
llege, said Dr. Luj=E1n's new finding "may be conceptually applicable to ma=
laria," although the malaria parasite does not use RNA interference and no =
one yet knows how to make it display all its 60 coat protein genes at once.=
<br>

<br>
A human vaccine for giardia could be of great benefit if the many mild case=
s in the developing world do in fact undermine health. Some experts believe=
 persistent giardia infection causes malnutrition, but others are less sure=
 of this.<br>

<br>
For the much smaller number of Westerners who are not inured to the disease=
, a vaccine would be a welcome addition to the few available drugs. It woul=
d have been a godsend for the Crusaders, who are known from historical acco=
unts to have suffered terribly from a variety of intestinal diseases that h=
ad no respect for rank. In 1249 King Louis IX, who led the Seventh Crusade,=
 had such serious diarrhea that part of the monarch's breeches were cut awa=
y to ease his personal hygiene. Giardia may well have been his tormentor. U=
sing a sensitive immunological test, researchers who excavated a medieval l=
atrine in the city of Acre, once part of the Crusader kingdom of Jerusalem,=
 detected the presence of giardia, they reported in the July issue of The J=
ournal of Archaeological Science.<br>

<br>
Giardia itself is far more ancient than any Crusader kingdom. Though a sing=
le-celled organism, it belongs to the eukaryotes, the domain that includes =
all plants and animals. In the tree of eukaryotic life, giardia belongs to =
one of the earliest branches. It lacks mitochondria, the energy-producing o=
rganelles that are almost a badge of eukaryote identity. Even stranger, eac=
h giardia cell possesses two nuclei; no one knows what benefit offsets the =
cost of maintaining the second. Before this enigmatic microbe plagued peopl=
e, it was doubtless the scourge of many earlier species. Dr. Luj=E1n's disc=
overy may be a critical step in curbing giardia's merciless torment of its =
fellow eukaryotes.<br>

<br>
health-vn List<br>
Bringing Millennium Development Goals Closer to the People<br>
email the list: &lt;<a href=3D"mailto:health...@cairo.anu.edu.au" target=3D=
"_blank">health...@cairo.anu.edu.au</a>&gt;<br>
To subscribe/unsubscribe contact: Vern Weitzel &lt;<a href=3D"mailto:vern@c=
oombs.anu.edu.au" target=3D"_blank">v...@coombs.anu.edu.au</a>&gt;<br>
Other lists: <a href=3D"http://coombs.anu.edu.au/%7Evern/forum.html" target=
=3D"_blank">http://coombs.anu.edu.au/~vern/forum.html</a><br>
<br>
The accuracy of information from media articles posted on this list<br>
cannot be guaranteed and should be verified before use. Your<br>
comments to the list on these stories are most welcome!<br>
</div><br><br clear=3D"all"><br>-- <br>_______________________<br>St=E9phan=
e P. Rousseau (Mr)<br>Regional Coordinator<br><br>Regional Coordination Uni=
t (RCU)<br>Asian Development Bank <br>Greater Mekong Communicable Diseases =
Control Project<br>
Room 2104, 21st Floor, <br>Thanh Cong Tower, <br>57 Lang Ha Street, <br>Ba =
Dinh District, Hanoi =96 VIET NAM<br><br>Tel: +84 (0) 43 514 79 33<br>Fax: =
+84 (0) 43 514 80 12<br>Email: <a href=3D"mailto:gms.cdc...@gmail.com">gms.=
cdc...@gmail.com</a> <br>
Website: <a href=3D"http://gms-cdc.org/index.php">http://gms-cdc.org/index.=
php</a><br>

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