Acidification Activates Motility and Egress by Enhancing Protein Secretion and Cytolytic Activity

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Toxoplasma and related parasites including those that cause malaria are obligate intracellular pathogens that replicate within a specialized compartment termed the parasitophorous vacuole. To infect new host cells these parasites must first escape from the parasitophorous vacuole and other limiting membranes of the currently infected cell. Escape, or egress as it is often called, depends on the timely release of adhesive proteins and lysis factors from secretory organelles called micronemes. Although this secretory event is crucial for egress, the natural environmental cues that trigger microneme secretion remain poorly defined. Here we discover that acidification of the parasitophorous vacuole is sufficient to trigger microneme secretion and promote the activity of a lysis factor called PLP1. We also show that pH-neutralizing drugs inhibit egress and provide evidence of parasitophorous vacuole acidification approximately coinciding with parasite egress from infected host cells. The findings support a working model in which acidification activates microneme dependent motility and lytic activity to execute egress and destruction of infected cells. The results also provide insight into how PLP1 lytic activity is stimulated during egress in an acidic environment and subsequently suppressed by the neutral extracellular environment, thus permitting cell invasion with minimal damage to the next target cell.

Vyšlo v časopise: Acidification Activates Motility and Egress by Enhancing Protein Secretion and Cytolytic Activity. PLoS Pathog 10(11): e32767. doi:10.1371/journal.ppat.1004488
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004488

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