Toxoplasmosis: propagation of parasite in host cell stopped
Published: 10 May 2022
Research led by the Institute of Infection, Immunity and Inflammation's Professor Markus Meißner has discovered a new method that blocks the protein regulation of the parasite Toxoplasma gondii and causes it to die off inside the host cell.
Research led by the Institute of Infection, Immunity and Inflammation's Professor Markus Meißner has discovered a new method that blocks the protein regulation of the parasite Toxoplasma gondii and causes it to die off inside the host cell.
An infectious disease that can be transmitted from cats to humans, Toxoplasmosis is one of the most widespread zoonoses worldwide.
People can also become infected by consuming raw or undercooked meat, and infection is particularly dangerous for pregnant women, as it can cause fetal deformities.
The cause of the disease is the single-celled parasite Toxoplasma gondii. Inside the host cell, it forms a little bubble-like compartment called a parasitophorous vacuole, which facilitates nutrient exchange and synchronized cell division.
The resulting daughter cells, of which up to 64 can form in the compartment, are connected with each other inside the vacuole via a network, somewhat akin to an umbilical cord.
As soon as the offspring are mature, a regulation mechanism prompts the dissolution of the vacuole and the structures that have formed inside it. This is the moment at which the daughter cells become mobile and invade new host cells.
Before now, it was not known which genes encode the proteins that control the exit from the host cell.
To identify them, a team led by Professor Meißner, Chair of Experimental Parasitology at Ludwig-Maximilians-Universität München (LMU) and Associate Professor at iii, collaborated with colleagues from the University of Glasgow to develop a novel genetic screening technique, which is based on the Cas9 'genetic scissors', and investigate a library of 320 parasite-specific genes.
They discovered two genes without which cell egress is impossible. The targeted destruction of these genes led to a blockade of the egress and thus to the death of the next generation of parasites within the host cell.
On the research, published in Nature Micriobology, Professor Meißner said: “This paves the way potentially for the development of active substances that could block the function of the corresponding proteins and so put a halt to propagation."
Toxoplasma gondii is closely related to the malaria pathogen Plasmodium falciparum. Therefore, the parasite serves as a model organism for the pathogen of the tropical disease, which kills hundreds of thousands of people worldwide every year.
LMU parasitologist Dr Elena Jimenez-Ruiz explained: “We assume that similar processes control the propagation of the malaria pathogen.
“Next, we will investigate what functions these proteins have in the malaria pathogen and whether there are possible starting points for the development of new drugs."
Toxoplasmosis: propagation of parasite in host cell stopped
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Wei Li, Janessa Grech, Johannes Felix Stortz, Matthew Gow, Javier Periz, Markus Meissner, and Elena Jimenez-Ruiz
- Published: 10 May 2022. Nature Micriobology
Image Legend: Scale bar showing intracellular parasites that are connected by the intravacuolar network. The disassembly of this network is one of the first crucial steps for the parasite to exit from the host cell.
First published: 10 May 2022