International Journal for Parasitology 17 "0887# 0904Ð0907
Structure and function of the parasitophorous vacuole in
Eimeria species
R[ Entzeroth\ F[R[ Mattig\ R[ Werner!Meier
Institute of Zoology\ University of Technology Dresden\ Mommsenstra)e 02\ 90951 Dresden\ Germany
Received 0 December 0886^ accepted 09 March 0887
Abstract
The intracellular life!cycle stages of Eimeria are located in the host cell within a membrane!bound parasitophorous
vacuole[ The invasion process and the formation of the parasitophorous vacuole are mediated by characteristic organelles
within the apical complex[ During invasion\ the parasitophorous!vacuole membrane is manipulated by the parasite and
functions later in the development cycle as a molecular sieve\ allowing the exchange of metabolites between parasite and
host cell[ Unlike the cyst!forming coccidia\ there is little evidence of parasitophorous!vacuole membrane transformation
in the later stages of the lifecycle of Eimeria species[ Compared with the human pathogens Plasmodium and Toxoplasma\
rather little is known about the parasitophorous vacuole and parasitophorous!vacuole membrane of animal pathogens
of the genus Eimeria[ Þ 0887 Australian Society for Parasitology[ Published by Elsevier Science Ltd[
Keywords] Parasitophorous vacuole "PV#^ Eimeria^ Parasite
0[ Introduction
Parasites of the genus Eimeria are obligatory
intracellular parasites mostly of intestinal cells\
although some live in other cells and:or organs of
invertebrates and vertebrates[ Coccidiosis of dom!
estic animals\ cattle and chickens is due to infection
with di}erent Eimeria spp[ and causes considerable
economic losses[ The animal!breeding industry
spends millions of dollars each year on measures to
control coccidiosis\ mainly anticoccidial drugs[
The intracellular life!cycle stages of Eimeria para!
sites\ including merozoites\ schizonts "meronts# and
gamonts\ are located within the host cell in a mem!
brane!bound parasitophorous vacuole "PV# ð0Ł[ The
Corresponding author[ Tel[] 9240:352! 6425^ fax] 9240:352!
6130[
PV membrane "PVM# is formed during invasion of
the motile stages of Eimeria parasites "sporozoites
and merozoites#[ The invasion of Eimeria spp[ is an
active process and resembles closely that in other
related species of Apicomplexa "Toxoplasma\ Plas!
modium#[ The PVM serves to protect the parasite
against lysis by the host cell\ but also constitutes a
barrier between the host!cell metabolites and the
parasite that depends on them[ Since Eimerian
parasites do not form cysts\ modi_cation of the
PVM is usually not observed[
1[ Organelles involved with invasion and
parasitophorous!vacuole formation
The invasion process of Eimeria by the motile
zoites is active\ and characteristic organelles from
within the apical complex "conoid\ polar rings\ mic!
S9919!6408:87 ,08[99¦9[99 Þ 0887 Australian Society for Parasitology[ Published by Elsevier Science Ltd[ Printed in Great Britain
PII] S9919!6408"87#99968!3
0905
R[ Entzeroth et al[ : International Journal for Parasitolo`y 17 "0887# 0904Ð0907
ronemes\ rhoptries and dense granules# are of func!
tional importance[ The function of the conoid and
polar rings is so far unknown[ Micronemes promote
the attachment of parasites to the potential host
cells ð1Ł[ The zoites come into contact with the epi!
thelial cell ð2\ 3Ł and micronemes secrete their pro!
tein contents\ which have been characterised ð1\ 4Ł[
The known sequences of some microneme proteins
ð5Ł are very similar within the di}erent apic!
omplexan species and indicate a common function[
There is also evidence that\ as well as the attachment
function\ micronemes are involved in motility since
microneme knock!out mutants in Plasmodium lose
the ability to move and invade host cell ð6Ł[ Rhop!
tries may have functions in the initial process of
PV formation during invasion ð7\ 8Ł and have been
shown to discharge their contents through a duct
into the forming parasitophorous vacuole[ In Tox!
oplasma at least 09 rhoptry proteins have been
identi_ed ð09Ł and some of these proteins "ROP 1\
2\ 3# are stably associated with the membrane lining
the PVM[ In Eimeria species\ rhoptry proteins have
been characterised in sporozoites of Eimeria tenella
ð00\ 01Ł and merozoites of Eimeria nieschulzi ð02Ł[
Using rhoptry!speci_c antibodies\ rhoptry proteins
from E[ tenella were shown to be associated with
the PVM ð00\ 01Ł and in E[ nieschulzi a 11!kDa
rhoptry protein was shown to be exocytosed into
the PV at invasion ð02Ł[ The total protein content
of rhoptries of Eimeria spp[ is very heterogeneous
ð03Ł and the protein contents may di}er between
rhoptries of sporozoites and merozoites from the
same species\ as indicated by rhoptry!speci_c anti!
bodies ð02\ 03Ł[ Dense granules are discharged after
invasion in the cyst!forming Coccidia "Sarcocystis\
Toxoplasma# and contribute to the modi_cation of
the PV and PVM in these species ð04Ł[ There is only
little evidence that dense granules exist in Eimeria
species ð05Ł and the function of this organelle is not
yet known[
2[ Transport across the parasitophorous!vacuole
membrane
The PVM in Toxoplasma is permeable for
charged and uncharged molecules of less than
0399 Da ð06Ł[ Microinjection experiments in host
cells infected with E[ nieschulzi have shown that
molecules of up to 749 Da can pass the PVM\ while
molecules of 09 999 Da are excluded from the PV
ð07Ł[ Similar results have been obtained in Plas!
modium[ The experiments give evidence that the
PVM may function as a molecular sieve[ Postulated
pores across the PVM probably provide nutritional
channels that allow the passive transfer of mol!
ecules to the parasite[
The function of duct!like structures within
infected host cells\ marked by rhoptry!speci_c mAb
ð08Ł\ is not yet known[ These structures resemble the
postulated {{parasitophorous duct|| in Plasmodium
ð19Ð11Ł\ which was claimed to allow the di}usion
even of macromolecules from the extracellular med!
ium into the parasitophorous vacuole[ Obviously\
the two models of transport into the PV are essen!
tially incompatible] if a direct connection "{{duct||#
existed together with pores in the PVM\ the host
cell would leak low molecular weight solutes into
the extracellular space[
The PVM in Toxoplasma!infected cells is fusion
incompetent for lysosomes\ protecting the parasite
from lytic enzymes ð12\ 13Ł[ No experiments have
been performed yet to show fusion incompetence
for the PVM in Eimeria!infected cells[
3[ Modi_cation of the parasitophorous vacuole
during the life!cycle of Eimeria
In cyst!forming Coccidia\ the PV is modi_ed
shortly after invasion[ In Toxoplasma an intra!
vacuolar network is formed with which secreted
proteins of dense granules become associated ð14Ł[
In Sarcocystis\ bradyzoites escape from the primary
PV and a secondary PV derived from host!cell
endoplasmic reticulum is formed and dense gran!
ules are exocytosed ð15Ł[
There is little evidence of transformation of the
PV in Eimeria[ The presence and exocytosis of dense
granules have been postulated in E[ tenella ð05Ł and
Eimeria papillata ð16Ł[ Electron!dense material has
been reported in the PV of several Eimeria species
ð17Ð29Ł[ Intravacuolar tubules are peculiar struc!
tures within the PV of Eimeria maxima mac!
rogamonts ð20Ł[ In E[ nieschulzi schizonts\ the PVM
bears {{microvilli|| protruding into the PV ð23Ł[
R[ Entzeroth et al[ : International Journal for Parasitolo`y 17 "0887# 0904Ð0907
After di}erentiation of merozoites in schizonts\
merozoites become active and leave the par!
asitophorous vacuole[ The mechanism of merozoite
release is poorly known\ and may be active or
passive[ Parasite proteases may be involved also in
Eimeria spp[ as documented in Plasmodium ð21\ 22Ł[
4[ Conclusion
The PV is a crucial structure in the life!cycle of
Coccidia\ although there are a few exceptions where
the PV is absent "Theileria\ Babesia\ certain stages
of Sarcocystis#[ The PV is manipulated by the para!
site and functions as a molecular sieve\ allowing the
exchange of metabolites between parasite and host
cell[ Compared with the human pathogens Plas!
modium and Toxoplasma\ rather little is known
about the animal pathogens of the genus Eimeria[
Understanding of the formation\ modi_cation and
function of the PV would facilitate the development
of agents interfering with the development of the
parasites[
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