2010-ASCB-Press-Book - page 6

T h e A m e r i c a n s o c i e t y f o r C e l l B i o l o g y
5
News from
The American Society
for Cell Biology
50th Annual Meeting
Philadelphia, PA
December 11–15, 2010
Obligates beneath the skin
EMBARGOED
FOR RELEASE
10:00 am, U.S. Eastern Time
Sunday, December 12, 2010
Contact
Julia D. Romano
Johns Hopkins Bloomberg
School of Public Health
615 N. Wolfe St., E2209
Baltimore, MD 21205
443-287-1588
Author presents
Sunday, December 12, 2010
11:30 am–1:00 pm
Session: Host–Pathogen
Interactions I
Exhibit Halls A/B/C
Program: 755
Board B1165
Co-Option of the Host Cell Golgi
by the Intracellular Parasite
Toxoplasma gondii
J.D. Romano, C. de Beaumont,
I. Coppens
Molecular Microbiology and
Immunology, Johns Hopkins
Bloomberg School of Public
Health, Baltimore, MD
S. Sonda
Institute of Parasitology,
University of Zurich, Zurich,
Switzerland
J.A. Carrasco, P.M. Bavoil
Department of Microbial
Pathogenesis, University of
Maryland Dental School,
Baltimore, MD
This work was supported by
National Institutes of Health
grant R01AI06767.
Two diverse pathogens,Toxoplasma
and Chlamydia, share a sickening
evolutionary trick
T
hey share a nasty reputation as
biological invaders and the label
“obligate pathogens,” meaning that
both
Toxoplasma gondii
and
Chlamydia
trachomatis
must reproduce within the
host—for these two, within a sealed vacu-
ole inside the host cells of their victims.
Yet the two disease agents would appear
to have little else in common:
T. gondii
is
a protozoan parasite, and the genus
Chla-
mydia
is a ubiquitous tribe of pathogenic
bacteria. But a probing new look at how
these invaders actually operate inside
human host cells reveals a startlingly
similar modus operandi. Researchers at
the Johns Hopkins Bloomberg School of
Public Health and colleagues elsewhere
say that both pathogens hijack the Golgi
apparatus of their host cells, reorganizing
that organelle into ministacks conve-
niently aligned just outside the invader’s
hiding place. This predatory similarity,
say Julia Romano and Isabelle Coppens
of Hopkins, is an example of conver-
gent evolution, as well as a possible clue
toward containing two of the most com-
mon infections on Earth.
Convergent evolution is the develop-
ment of a similar biological trait in unre-
lated lineages, such as the way bats and
toothed whales independently came up
with echolocation for hunting. Protozoa
and bacteria stem from distant evolu-
tionary branches, yet when the Hopkins
researchers and colleagues from the Uni-
versity of Maryland Dental School and
the University of Zurich (Switzerland)
looked at how
Toxoplasma
secures a
nutrient supply inside an infected host,
The host Golgi (green) is fragmented and surrounds the parasite’s vacuole (red) in a mammalian cell infected with
Toxoplasma gondii for 24 hours. HeLa cells were infected with Toxoplasma gondii for 24 hours. Cells were fixed
and processed for immunofluorescence using antibodies against the Golgi marker giantin (green) and the parasite
vacuole marker TgGRA7 (red). Images were acquired as a z-stack of optical sections. (A) A phase contrast image
of an infected cell. The scale bar is 10µm. (B) An extended focus image of infected cells. The scale bar is 10µm.
they noticed a strong parallel with chla-
mydial infection—both target the host
cell’s Golgi apparatus. The “post office
of the cell,” the Golgi body packs up and
dispatches cellular cargoes, such as lipids,
in sealed vacuoles.
In work supported by the National In-
stitutes of Health, Romano and Coppens
studied
Toxoplasma
-infected host cells
to see how the parasite hijacked lipids
called ceramides. To hide from attack by
the host’s immune system, the protozoan
must live inside its own capsule, called
a parasitophorous vacuole (PV), and yet
be able to grab nutrients without expos-
ing itself.
Toxoplasma,
the researchers
discovered, locates its PV near the hub of
the cell’s cargo system, the pericentriolar
region, and thus close to the Golgi appa-
ratus. Within 32 hours of infecting a host
cell, the protozoan had sliced the Golgi
into fragmented minidisks and was in-
gesting intact vacuoles containing cer-
amides through its PV membrane.
The remodeled Golgi, the PV’s loca-
tion in the pericentriolar region, and the
efficient capture of the host’s sphingo-
lipid supply all strongly reminded the
researchers of infection by
C. trachomatis,
the most frequently reported sexually
transmitted disease in America. To test
the parallel, the researchers coinfected
mammalian cells with
Toxoplasma
and
C.
trachomatis.
The two pathogens quickly
divided the Golgi between them, dis-
tributing the fragments of the organelle
equally, a startling demonstration of how
two disparate pathogens can agree on a
common evolutionary strategy.
According to the Centers for Disease
Control and Prevention (CDC), there were
1.2 million reported cases of
C. trachoma-
tis
infection in the U.S. in 2008.
It is particularly dangerous in
women, where untreated “silent”
C. trachomatis
infections can cause
infertility. Spread by infected meat,
toxoplasmosis is the third-leading
cause of death due to foodborne
illness in the U.S., according to the
CDC.
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