Human African Trypanosomiasis, also known as sleeping sickness, is one of the deadlier diseases in sub–Saharan Africa. It is caused by the African trypanosome parasite and is transmitted to humans through the bite of a tsetse fly. Few methods currently exist to combat this tropical disease that afflicts tens of thousands of people annually and also attacks livestock, preventing many rural poor from achieving even subsistence–level farming.
The key to slowing, and perhaps eventually eliminating, the disease might be found in a protein that the fly produces.
Tsetse flies carry the vital bacteria, Wigglesworthia glossinidiae, in their guts. This bacteria produce necessary vitamins that the fly does not otherwise receive from its sole diet of invertebrate blood. Without the vitamins the tsetse fly cannot reproduce. And while tsetse flies can naturally eliminate various bacterial infections, the mechanisms that allow the fly to tolerate beneficial Wigglesworthia are not understood.
The laboratory of Serap Aksoy, Ph.D., professor and head of the division of Epidemiology of Microbial Diseases at the Yale School of Public Health, is conducting research to develop insect–based methods to combat the disease’s transmission. Recent research by her lab showed that in the absence of the beneficial Wigglesworthia, tsetse flies were not only sterile but were much better at transmitting disease–causing trypanosome parasites.
Aksoy’s team recently reported in the journal PNAS that they identified a protein that appears to play an important role in the symbiotic relationship between the fly and Wigglesworthia. To protect its obligate bacteria, the tsetse fly synthesizes a Peptidoglycan Recognition Protein (PGRP) that eliminates the immunogenic peptidoglycan released by Wigglesworthia. The research showed that eliminating this PGRP induces the tsetse fly’s immune responses, which in turn damage Wigglesworthia. Unexpectedly, reduction of PGRP also increased parasite survival in flies. Thus the team’s research suggest that tsetse’s PGRP plays a dual role: it provides protection to Wigglesworthia by preventing the induction of damaging host immune responses and it eliminates parasite infections that can reduce tsetse’s fecundity.
The discovery offers several potentially novel and effective approaches to control a disease that remains a scourge in much of Africa. Aksoy said that approaches that eliminate Wigglesworthia are desirable as they could result in fewer tsetse flies to transmit the disease. An alternative approach, which the group is now exploring, is to overexpress the trypanolytic PGRP in tsetse flies. The group will do this by splicing the PGRP gene into tsetse’s commensal bacteria Sodalis, which resides in the gut of the fly where parasitic trypanosomes replicate. The group expects that higher levels of PGRP in the gut will prevent parasite survival. The hope is then to use these engineered parasite–resistant flies to replace their susceptible counterparts in nature.
The research team also included YSPH postdoctoral fellows Jingwen Wang and Guangxiao Yang and lab assistant Yineng Wu.