Aspartyl proteasesinToxoplasma

gondii andPlasmodiumfalciparum

meBOP-ModuleII

DimaElSafadiImen MkadaAssef Hamdan

Apicomplexa

Piroplasmida

Haemosporida

Coccidia

Plasmodium spp

Theileriidiae

Babesiidae

Theileria

Babesia

Eimeriidae

Cryptosporidiidae

Sarcocystidae

EimeriidaEimeria

Cryptosporidium spp

Sarcocystis

Toxoplasma

Neospora

Malaria

Toxoplasmosis

cryptosporidiosis

East coast fever

Coccidiosis

Apicomplexans are human and animal pathogens

LifeCycleof Plasmodium– HumanCycle

LifeCycleof Toxoplasma – HumanCycle

Apicomplexan ASPs follow 6 distinct groups

TgASP3

PM1,2,4,HAPTgASP1

PMV

TgASP7

TgASP5

TgASP2

TgASP6

PMVII

PMVIII

PMVI

PMX

PMIX

TgASP4

PlasmodiumspecificHemoglobindegradation

D

C

BE

AF

ProteinexportPV/PVM

?

?

?

ASP3Knockdowninduciblesystem(Asp3-iKD)

• Intracellularparasites

• ASP3Knockout→lytic cycleofparasite(ASP3playanimportantroleinthelifecycle)

• ASP3Knockdowninduciblesystem(Asp3-iKD)

-ATC

Δku80

+ATC

Asp3-iKD

7days

PlaqueAssay

ASP3knockdowndisplaysaseverelyticcycledefect

Glidingmotility

Egress

Invasion

Intracellulargrowth

Attachment

CellLysis