Circadian control in sleeping sickness parasite uncovered

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The parasite responsible for sleeping sickness, Trypanosoma brucei, has its own internal molecular clock, according to new collaborative research from the University of Lisbon (Portugal) and Southwestern University (TX, USA). The team demonstrated that circadian oscillations were associated with differences in drug sensitivity; these findings could be utilized to improve treatment efficiency for this disease.

Sleeping sickness is often fatal, currently no vaccines are available and many treatments have complications, such as toxicity; however, the WHO is aiming to eliminate the disease by 2020, making research in this area pressing.

It has previously been reported that within a host, parasitic infection can interfere with the host circadian clock; in addition, daily rhythms have been observed in parasites residing in a host. This study, published recently in Nature Microbiology, aimed to elucidate whether the circadian rhythms observed in Trypanosoma brucei were caused by responding to host physiological cues or whether the parasites possess intrinsic molecular clocks.

The team studied the parasite in vitro, ensuring the parasites where synchronized to the time of day before sequencing their transcriptome. The researchers utilized bioinformatics to analyze gene expression in the parasites reporting that in vitro approximately 10% of T. brucei genes were expressed in a circadian rhythm. This demonstrates the parasites have an intrinsic clock and their metabolism is under some circadian control.

In addition, the group observed that daily fluctuations led to differences in sensitivity to suramin, a drug commonly utilized to treat sleeping sickness. This information could help to improve the efficiency of current treatments as administering drugs in the evening, when sensitivity is higher, could be more effective.

Senior Author Luísa Figueiredo, from the University of Lisbon, concluded: “In the future we can administer this drug at certain hours of the day because now we know that it will be more efficient. This concept of administering a therapy at a specific hour, known as chronotherapy, is already applied to other pathologies, namely asthma and cancer. However, it has never been applied in the treatment of infectious diseases.”

Source: Rijo-Ferreira F, Pinto-Neves D, Barbosa-Morais NL, Takahashi JS & Figueiredo LM. Trypanosoma brucei metabolism is under circadian control. Nat. Microbiol. 2 (17032) (2017); www.eurekalert.org/pub_releases/2017-03/idmm-ttt031317.php

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