The parasite that causes deadly sleeping sickness has its own biological clock that makes it more vulnerable to medications during the afternoon, according to international research that may help improve treatments for one of Africa's most lethal diseases.
"This research has opened a door," said, first author of the study. "If the same therapeutic effect can be obtained with a lower dose, then it may be possible to reduce the mortality associated with the treatment."
Establishing that parasites have their own internal clock is a key step in finding new ways to treat a variety of parasitic conditions, from sleeping sickness to malaria. While many of these diseases are often not deadly, sleeping sickness has been among the most lethal.
The condition - known formally as African trypanosomiasis - is transmitted through the bite of the Tsetse fly and threatens tens of millions of people in sub-Saharan African countries. After entering the body, the parasite causes such symptoms as inverted sleeping cycles, fever, muscle weakness, and itching. It eventually invades the central nervous system and, depending on its type, can kill its host in anywhere from a few months to several years.
Control efforts have significantly reduced the number of cases over the last decade. However, an unknown number of people still die annually from sleeping sickness as scientists continue seeking a vaccine and alternative treatments to the arsenic-based medications that are occasionally fatal to patients.
The authors found that in vitro, ∼10% of genes in T. brucei are expressed with a circadian rhythm. The maximum expression of these genes occurs at two different phases of the day and may depend on a post-transcriptional mechanism.
Circadian genes are enriched in cellular metabolic pathways and coincide with two peaks of intracellular adenosine triphosphate concentration. Moreover, daily changes in the parasite population lead to differences in suramin sensitivity, a drug commonly used to treat this infection.
The senior author of the collaborative study published in Nature Microbiology said the finding will likely apply to all types of parasites and perhaps lead to improved treatment for their associated conditions.
"There have been many observations of the presence of daily patterns in parasites, but until now we didn't know if this was the result of an intrinsic molecular clock. In the future, we may consider biological rhythms when defining therapies to treat sleeping sickness and potentially other infections," said the senior author.
Parasites biologic clock found!
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