Obligatory Intracellular Parasitism: Cell Biological Adaptations of Apicomplexan Parasites Inside Mammalian Cells
The Coppens laboratory is conducting research at the forefront of the exciting arena of host-parasite interactions. The phylum Apicomplexa includes a large number of intracellular protozoan parasites that must live in a membrane-bound compartment in mammalian cells in order to survive. Among these are some notorious human and animal pathogens such as Plasmodium, the causative agent of malaria, and Toxoplasma and Cryptosporidium, two leading opportunistic pathogens in immunosuppressive conditions. Apicomplexa infections are wide-spread, life-threatening and still therapeutically challenging.
By entering into the confines of a cell, these parasites assure themselves a ready source of nutrients and protection from immune confrontations. This luxury crucially relies upon the successful entry into a target cell and the avoidance of host cell defenses such as acidification and endo-lysosomal hydrolases. Unarguably, Apicomplexa are highly competent to establish a nonfusogenic parasitophorous vacuole (PV) that provides a balance between the subversion of host defenses and the parasite's anabolic needs. We are studying the strategies used by Apicomplexa to adapt and exploit their mammalian host cells, leading to disease pathology. Because of the abundance of organic molecules within mammalian cells, these parasites have lost many genes required for the biosynthesis of vital components. In return, novel genes promoting host nutrient scavenging have become essential, and constitute a successful scenario for achieving pathogenicity. The original features discovered through the study of intracellular parasitism offer a unique perspective for elucidating basic questions in mammalian cell biology. In many instances, Apicomplexa have challenged dogma thought to be universal in eukaryotic biology.
- Apicomplexa: Toxoplasma, Plasmodium liver stage, Cryptosporidium
- Drug target discovery
- Host organelle-parasite interaction
- Intracellular parasitism
- Lipid uptake
- Live attenuated malaria vaccine
- Plasmodium metamorphosis
EM image showing two large lipid droplets containing cholesterol stores in Cryptosporidium infecting enterocytes
MANIPULATING THE HOST CELL
Fluorescence image showing Toxoplasma (purple) sequestering host Rab11 vesicles (green) inside a parasitophorous vacuole (blue).
SPOROZOITE TRANSFORMING TO TROPHOZOITE
Scanning EM showing sporozoite (insect form) undergoing morphological transformations to become a round trophozoite (liver forms) prior to replication
Isabelle Coppens, PhD, Professor
Department of Molecular Microbiology & Immunology
Johns Hopkins Bloomberg School of Public Health
615 N. Wolfe Street
E2209 (lab) E5648 (office)
Baltimore, MD 21205