Anin vivofitness gene ofToxoplasma, MIC11, is essential for PLP1-mediated egress from host cells DOI Creative Commons
Yuta Tachibana, Miwa Sasai, Hidetaka Kosako

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Summary After invasion and replication, intracellular pathogens must egress from infected host cells . Toxoplasma gondii facilitates this process by permeabilizing releasing perforin-like protein 1 (PLP1) through induced microneme secretion. However, the precise mechanism of cell permeabilization remains enigmatic. Here, we identified secretory MIC11 as a key factor for membrane disruption. A CRISPR-based in vivo screen revealed several genes including an essential gene virulence. Deletion resulted severe defects both rupture egress. Scanning mutagenesis functional motifs MIC11, mechanistic analyses demonstrated that directly associates with PLP1, regulating its activity The paralogue MIC22 compensated deletion, suggesting conserved feline-restricted stages T. discovery advances understanding how parasites disrupt to facilitate rapid successful dissemination.

Language: Английский

A CRISPR view on genetic screens in Toxoplasma gondii DOI Creative Commons
Franziska Hildebrandt, Ana Catarina Matias, Moritz Treeck

et al.

Current Opinion in Microbiology, Journal Year: 2025, Volume and Issue: 83, P. 102577 - 102577

Published: Jan. 8, 2025

Genome editing technologies, such as CRISPR-Cas9, have revolutionised the study of genes in a variety organisms, including unicellular parasites. Today, CRISPR-Cas9 technology is vastly applied high-throughput screens to investigate interactions between Apicomplexan parasite Toxoplasma gondii and its hosts. In vitro vivo T. performed naive restrictive conditions led discovery essential fitness-conferring genes, well factors important for virulence dissemination. Recent studies adapted screening based on phenotypes unrelated survival. These advances were achieved by using conditional systems coupled with imaging, single-cell RNA sequencing phenotypic selection. Here, we review state-of-the-art technologies focus gondii, highlighting strengths, current limitations future avenues development, application other species.

Language: Английский

Citations

1
The Importance of Translational Research in the Study of Ocular Toxoplasmosis; Insights from the 17th International Congress on Toxoplasmosis 2024 DOI Creative Commons
Alejandra de‐la‐Torre, Germán Mejía‐Salgado, Gereon Schares

et al.

FEMS Microbes, Journal Year: 2025, Volume and Issue: 6

Published: Jan. 1, 2025

Abstract Toxoplasmosis is a parasitic infection with significant implications for human health, particularly in its ocular form, which can lead to severe visual impairment. While both basic and clinical research have made considerable strides understanding the biology treatment of this parasite, challenges remain. Recent advancements diagnostics, mainly through multimodal imaging, improved identification active disease predicting outcomes. Experimental therapies are also emerging, offering new hope more effective treatments. However, most critical insight from recent research, emphasized at 17th International Congress on Toxoplasmosis, necessity collaborative approach. Integrating essential translating molecular pathophysiological findings into practices. This synergy crucial advancing strategies improving patient outcomes toxoplasmosis.

Language: Английский

Citations

0
Anin vivofitness gene ofToxoplasma, MIC11, is essential for PLP1-mediated egress from host cells DOI Creative Commons
Yuta Tachibana, Miwa Sasai, Hidetaka Kosako

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Summary After invasion and replication, intracellular pathogens must egress from infected host cells . Toxoplasma gondii facilitates this process by permeabilizing releasing perforin-like protein 1 (PLP1) through induced microneme secretion. However, the precise mechanism of cell permeabilization remains enigmatic. Here, we identified secretory MIC11 as a key factor for membrane disruption. A CRISPR-based in vivo screen revealed several genes including an essential gene virulence. Deletion resulted severe defects both rupture egress. Scanning mutagenesis functional motifs MIC11, mechanistic analyses demonstrated that directly associates with PLP1, regulating its activity The paralogue MIC22 compensated deletion, suggesting conserved feline-restricted stages T. discovery advances understanding how parasites disrupt to facilitate rapid successful dissemination.

Language: Английский

Citations

0