NIAB scientists perform CRISPR-based genetic manipulation to identify protein to halt zoonotic infection ‘Toxoplasmosis’

Research on Toxoplasmosis reveals potential vaccine strategy targeting essential splicing protein, offering protection against infection.

Toxoplasmosis is a parasitic zoonotic infection that can be transmitted through contaminated food, especially undercooked meat. The parasitic infection caused by ‘Toxoplasma gondii’ can lead to abortion and neonatal mortality in both humans and animals, causing substantial economic losses in the livestock industry due to reproductive failure.

The World Health Organisation (WHO) and Food & Agriculture Organisation (FAO) have ranked it as the fourth among food-borne infections of major concern. The infection is endemic in India, with a reported seroprevalence of above 20% in humans and animals. Overall, the Indian climate is said to be conducive to spreading the infection.

In this context, the latest research study by the laboratory of Abhijit S. Deshmukh in the National Institute of Animal Biotechnology (NIAB) assumes significance. Mr. Deshmukh and his team — Poonam Kashyap and Kalyani R. Aswale — performed CRISPR-based genetic manipulation on the parasite ‘Toxoplasma gondii’ and demonstrated that depleting the essential splicing protein — called ‘Cdc5’ — disrupts the RNA splicing process, leading to complete arrest of parasite replication.

Toxoplasma’s genome is rich in introns or non-coding DNA sequences, making efficient splicing crucial. The splicing factor protein ‘Cdc5’ is essential for the parasite’s survival. Depletion of TgCdc5 leads to erroneous splicing, causing catastrophic effects on the parasites. Experiments conducted on the mouse in the NIAB lab here in Hyderabad had shown that these splicing-deficient parasites lacking the key protein undergo an unproductive stage transition.

The researchers found that it has been leading to a slower-growing stage that elicits a robust immune response in the mouse host and protects them from future toxoplasma infections. “When the protein ‘TgCdc5’ is depleted upon the parasite infection in mice, these mice generate a protective immunity not only for future infections but also in providing partial protection during pregnancy. These findings suggest that targeting ‘TgCdc5’ protein could be a viable vaccine strategy for toxoplasmosis,“ said Mr. Deshmukh.

The disease is presently treated by a combination of Pyrimethamine, Sulfadiazine, and Clindamycin drugs. The infection causes more severe pathology in small ruminants like sheep and goats through ingestion of contaminated food and water, explained the scientist who has been studying the parasite for the last 10 years.

Published in the latest issue of the journal Nature Communications, the research work provides valuable information to strategize vaccine development for Toxoplasmosis, said NIAB Director G. Taru Sharma. The Biotechnology Research and Innovative Council (BRIC)-NIAB is an autonomous institute under the Department of Biotechnology (DBT) under the Ministry of Science & Technology.