Human parasite’s daily rhythms could be targeted for better treatments

The parasitic worm that causes the neglected tropical disease, schistosomiasis, has daily rhythms in gene expression, including genes that could be targeted in drug development.

For the first time, the worm that causes schistosomiasis has been shown to have a daily rhythm that impacts which genes are switched on at different times.

The new research, from the Wellcome Sanger Institute and collaborators, identified certain genes that are switched on in the parasite to align with the mouse host’s daily rhythms. This gives novel insights into how these centimetre long worms can survive the 24-hour cycles of the immune and blood-clotting systems in the human blood vessels for over 30 years¹.

Image credit: Rawlinson et al.

The study, published in BMC Biology, highlights that many genes that could be targeted in the development of treatments and vaccines for schistosomiasis have 24-hour patterns of expression. It suggests that there are certain times of the 24 hour period where these treatments could be more effective, when aligned with peak gene activity in the worm.

Schistosomiasis is a neglected tropical disease caused by the eggs of the female parasitic worm, Schistosoma mansoni. This disease has a vast human impact, causing an estimated 140,000 cases and 11,500 deaths in 2019 alone². It is prevalent across sub-Saharan Africa, certain South American countries and the Caribbean, with some reports in the Arabian Peninsula³. Despite the profound global impact of schistosomiasis, there is complete reliance on a single drug for treatment, and new evidence suggests that there is growing drug resistance in some worm populations^4,5. Therefore, there is a need to develop a new generation of therapeutics.

The cycle of day and night, imposed by the Earth turning on its axis, is one of the most striking features of the world in which we live. To align with this, many species exhibit daily changes in their behaviour and/or physiology. The synchrony of an organism with the environment is critical to its survival, and a mismatch in this can lead to the organism being unable to survive.

Disease-causing single celled parasites, such as Plasmodium parasites that live in mosquitoes and humans and cause malaria, have been proven to have daily rhythms in gene expression and these have been shown to impact drug sensitivity^6-8. However, it has never been studied in a multi-celled parasite like Schistosoma mansoni before.

In this new study, researchers collected worm samples from three infected mice every four hours over a 44 to 48 hour period. The gene expression of the worms was analysed over the time course and 209 genes were revealed to have 24-hour patterns of abundance. The function of these genes suggest that when the host is active the parasite is stressed, switching on genes that help protect the parasite from the rise of the host’s body temperature. Comparatively, during the host’s resting phase the parasite interacts with the host’s immune and blood coagulating systems and experiences a rush in activity of genes involved in changing food into energy.

This study also found that many genes expressed in the female reproductive system and involved in egg laying have daily rhythms of expression, and these translated to daily patterns of egg laying. Some of these genes could be targeted to provide new therapies to help treat schistosomiasis.

Tracking when these genes are switched on, and the mechanisms behind this, could be utilised to ensure that the treatments or vaccines are given when the gene is most active to ensure optimum effectiveness of treatments.

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Source: Sanger Institute