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

Marijo S. Roiko, Nadezhda Svezhova, Vern B. Carruthers.

PLoS Pathog (2014) 10(11): e1004488

Speaker: Jian-Ming Huang (黃建銘)           Time: 15:00~16:00, Apr. 29, 2015

Commentator: Dr. Chih-Li Hsu (胥直利 老師)  Place: Room 601

Abstract:

        Toxoplasma gondii is an intracelluar and parasitic protozoan that causes the disease toxoplasmosis. In the United States and the United Kingdom, it is estimated that 16–40% of the population are infected, whereas in Central and South America and continental Europe, estimates of infection range from 50 to 80% [1]. By and large, T. gondii is capable of infecting virtually all warm-blooded animals like humans. To infect new host cells, T. gondii first escapes from the parasitophorous vacuole and other limiting membranes of the currently infected cell. Although most infections in humans are asymptomatic, the parasite can produce devastating disease such as retino-choroiditis, hydrocephalus, convulsions and intracerebral calcification [2]. Therefore, it is important for the authors to realize pathogenesis about T. gondii including host cell invasion and egress. Previous study showed that T. gondii motility is pH-dependent [3]. The authors found that acidification of the parasitophorous vacuole is sufficient to trigger microneme secretion and promote the activity of a cytolysis factor called perforin-like protein 1 (PLP1), a pore-forming protein required for efficient egress. On the contrary, the authors showed that pH-neutralizing drugs such as NH₄Cl and DCCD, a P-type ATPase inhibitor, suppresse parasite egress and PLP1 activity. Finally, using erythrocytes as a measure of hemolysis and PLP1 membrane binding activity, the authors observed that they were all pH-dependent at acidic pH than neutral pH. In conclusion, low pH activates T. gondii motility and egress.

References:

1.         Dubey, J.P., et al., Toxoplasmosis in humans and animals in Brazil: high prevalence, high burden of disease, and epidemiology. Parasitology, 2012. 139(11): p. 1375-424.

2.         Wong, S.Y. and J.S. Remington, Toxoplasmosis in pregnancy. Clin Infect Dis, 1994. 18(6): p. 853-61; quiz 862.

3.         Endo, T., et al., Effects of extracellular potassium on acid release and motility initiation in Toxoplasma gondii. J Protozool, 1987. 34(3): p. 291-5.