scholarly journals Surface Sialic Acids Taken from the Host Allow Trypanosome Survival in Tsetse Fly Vectors

2004 ◽  
Vol 199 (10) ◽  
pp. 1445-1450 ◽  
Author(s):  
Kisaburo Nagamune ◽  
Alvaro Acosta-Serrano ◽  
Haruki Uemura ◽  
Reto Brun ◽  
Christina Kunz-Renggli ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Trypanosoma Brucei ◽  
Sialic Acids ◽  
Sleeping Sickness ◽  
Tsetse Fly ◽  
Mammalian Host ◽  
Tsetse Flies ◽  
African Trypanosome ◽  
Blood Sucking

The African trypanosome Trypanosoma brucei, which causes sleeping sickness in humans and Nagana disease in livestock, is spread via blood-sucking Tsetse flies. In the fly's intestine, the trypanosomes survive digestive and trypanocidal environments, proliferate, and translocate into the salivary gland, where they become infectious to the next mammalian host. Here, we show that for successful survival in Tsetse flies, the trypanosomes use trans-sialidase to transfer sialic acids that they cannot synthesize from host's glycoconjugates to the glycosylphosphatidylinositols (GPIs), which are abundantly expressed on their surface. Trypanosomes lacking sialic acids due to a defective generation of GPI-anchored trans-sialidase could not survive in the intestine, but regained the ability to survive when sialylated by means of soluble trans-sialidase. Thus, surface sialic acids appear to protect the parasites from the digestive and trypanocidal environments in the midgut of Tsetse flies.

scholarly journals Evolutionary diversification of the trypanosome haptoglobin-haemoglobin receptor from an ancestral haemoglobin receptor

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Harriet Lane-Serff ◽  
Paula MacGregor ◽  
Lori Peacock ◽  
Olivia JS Macleod ◽  
Christopher Kay ◽  
...  
Keyword(s):  
Developmental Stage ◽  
Trypanosoma Brucei ◽  
Evolutionary History ◽  
Trypanosoma Congolense ◽  
Tsetse Fly ◽  
Mammalian Host ◽  
Trypanosome Species ◽  
African Trypanosome ◽  
Evolutionary Diversification ◽  
Cellular Changes

The haptoglobin-haemoglobin receptor of the African trypanosome species, Trypanosoma brucei, is expressed when the parasite is in the bloodstream of the mammalian host, allowing it to acquire haem through the uptake of haptoglobin-haemoglobin complexes. Here we show that in Trypanosoma congolense this receptor is instead expressed in the epimastigote developmental stage that occurs in the tsetse fly, where it acts as a haemoglobin receptor. We also present the structure of the T. congolense receptor in complex with haemoglobin. This allows us to propose an evolutionary history for this receptor, charting the structural and cellular changes that took place as it adapted from a role in the insect to a new role in the mammalian host.

scholarly journals Oxidative phosphorylation is required for powering motility and development of the sleeping sickness parasite Trypanosoma brucei within the tsetse fly vector

2021 ◽  
Author(s):  
Caroline E Dewar ◽  
Aitor Casas-Sánchez ◽  
Constentin Dieme ◽  
Aline Crouzols ◽  
Lee Haines ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Trypanosoma Brucei ◽  
Atp Synthase ◽  
Sleeping Sickness ◽  
Tsetse Fly ◽  
Tsetse Flies ◽  
Respiratory Chain Complexes ◽  
Atp Production

The single-celled parasite Trypanosoma brucei causes sleeping sickness in humans and nagana in livestock and is transmitted by hematophagous tsetse flies. Lifecycle progression from mammalian bloodstream form to tsetse midgut form and, subsequently, infective salivary gland form depends on complex developmental steps and migration within different fly tissues. As the parasite colonises the glucose-poor insect midgut, its ATP production is thought to depend on activation of mitochondrial amino acid catabolism via oxidative phosphorylation. This process involves respiratory chain complexes and the F1FO-ATP synthase, and it requires protein subunits of these complexes that are encoded in the parasite's mitochondrial DNA (kinetoplast or kDNA). Here we show that a progressive loss of kDNA-encoded functions correlates with an increasingly impaired ability of T. brucei to initiate and complete its development in the tsetse. First, parasites with a mutated F1FO-ATP synthase with a reduced capacity for oxidative phosphorylation can initiate differentiation from bloodstream to insect form, but they are unable to proliferate in vitro. Unexpectedly, these cells can still colonise the tsetse midgut. However, these parasites exhibit a motility defect and are severely impaired in colonising or migrating to subsequent tsetse tissues. Second, parasites with a fully disrupted F1FO-ATP synthase complex that is completely unable to produce ATP by oxidative phosphorylation can still differentiate to the first insect stage in vitro but die within a few days and cannot establish a midgut infection in vivo. Third, mutant parasites lacking kDNA entirely can initiate differentiation but die within 24 h. Together, these three scenarios show that efficient ATP production via oxidative phosphorylation is not essential for initial colonisation of the tsetse vector, but it is required to power trypanosome migration within the fly.

scholarly journals Oxidative Phosphorylation Is Required for Powering Motility and Development of the Sleeping Sickness Parasite Trypanosoma brucei in the Tsetse Fly Vector

mBio ◽  
2022 ◽  
Author(s):  
Caroline E. Dewar ◽  
Aitor Casas-Sanchez ◽  
Constentin Dieme ◽  
Aline Crouzols ◽  
Lee R. Haines ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Salivary Glands ◽  
Trypanosoma Brucei ◽  
Blood Meal ◽  
Sleeping Sickness ◽  
Tsetse Fly ◽  
Tsetse Flies ◽  
African Trypanosomes ◽  
Complex Development

African trypanosomes cause disease in humans and their livestock and are transmitted by tsetse flies. The insect ingests these parasites with its blood meal, but to be transmitted to another mammal, the trypanosome must undergo complex development within the tsetse fly and migrate from the insect's gut to its salivary glands.

Basic Biology of Trypanosoma brucei with reference to the development of chemotherapies

2021 ◽  
Vol 27 ◽  
Author(s):  
Samuel Dean
Keyword(s):  
Trypanosoma Brucei ◽  
Late Stage ◽  
Antigenic Variation ◽  
Molecular Genetic ◽  
Sleeping Sickness ◽  
Tsetse Fly ◽  
Tsetse Flies ◽  
African Sleeping Sickness ◽  
Stage Disease ◽  
Late Stage Disease

: Trypanosoma brucei are protozoan parasites that causes the lethal human disease African sleeping sickness, and the economically devastating disease of cattle, Nagana. African sleeping sickness, or Human African Trypanosomiasis (HAT) threatens 65 million people, and animal trypanosomiasis makes large areas of farmland unusable. There is no vaccine and licenced therapies against the most severe, late-stage disease are toxic, impractical and ineffective. Trypanosomes are transmitted by tsetse flies and HAT is therefore predominantly confined to the tsetse fly belt in subSaharan African. They are exclusively extracellular, and they differentiate between at least seven developmental forms that are highly adapted to host and vector niches. In the mammalian (human) host they inhabit the blood, cerebrospinal fluid (late stage disease), skin and adipose fat. In the tsetse fly vector, they travel from the tsetse midgut to the salivary glands via the ectoperitrophic space and proventriculus. Trypanosomes are evolutionarily divergent compared with most branches of eukaryotic life. Perhaps most famous for their extraordinary mechanisms of monoallelic gene expression and antigenic variation, they have also been investigated because much of their biology is either highly unconventional or extreme. Moreover, in addition to their importance as pathogens, many researchers have been attracted to the field because trypanosomes have some of the most advanced molecular genetic tools and database resources of any model system. The following will cover just some aspects of trypanosome biology and how its divergent biochemistry has been leveraged to develop drugs to treat African Sleeping sickness. It is by no means intended to be a comprehensive survey of trypanosome features. Rather, it is hoped that it will present trypanosomes as one of the most fascinating and tractable systems in which to do discovery biology.

scholarly journals Game and Tsetse Fly in Southern Rhodesia

Oryx ◽  
1956 ◽  
Vol 3 (5) ◽  
pp. 259-265
Keyword(s):  
Nineteenth Century ◽  
Sleeping Sickness ◽  
Tsetse Fly ◽  
Tsetse Flies ◽  
Blood Sucking ◽  
Southern Rhodesia

Until nearly the end of the nineteenth century about two-thirds of Southern Rhodesia was uninhabitable by domestic cattle, and thus, to a great extent, unusable by mankind whether European or native, because of the disease trypanosomiasis. In man this is called sleeping sickness, in cattle nagana. It is caused by trypanosomes, minute organisms which live in the blood of the victims of the disease. These trypanosomes are sucked up, with the blood of the infected man or beast, by blood-sucking tsetse flies, develop in the fly and may be transmitted to the next creature on which the fly feeds.

scholarly journals Metabolic reprogramming during the Trypanosoma brucei life cycle

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 683 ◽  
Author(s):  
Terry K. Smith ◽  
Frédéric Bringaud ◽  
Derek P. Nolan ◽  
Luisa M. Figueiredo
Keyword(s):  
Life Cycle ◽  
Trypanosoma Brucei ◽  
Model Organism ◽  
Protozoan Parasite ◽  
Tsetse Fly ◽  
Metabolic Reprogramming ◽  
Mammalian Host ◽  
Insect Vector ◽  
Environmental Signals ◽  
Cellular Metabolic Activity

Cellular metabolic activity is a highly complex, dynamic, regulated process that is influenced by numerous factors, including extracellular environmental signals, nutrient availability and the physiological and developmental status of the cell. The causative agent of sleeping sickness, Trypanosoma brucei, is an exclusively extracellular protozoan parasite that encounters very different extracellular environments during its life cycle within the mammalian host and tsetse fly insect vector. In order to meet these challenges, there are significant alterations in the major energetic and metabolic pathways of these highly adaptable parasites. This review highlights some of these metabolic changes in this early divergent eukaryotic model organism.

scholarly journals Differential virulence and tsetse fly transmissibility of Trypanosoma congolense and Trypanosoma brucei strains

2017 ◽  
Vol 84 (1) ◽  
Author(s):  
Purity K. Gitonga ◽  
Kariuki Ndung’u ◽  
Grace A. Murilla ◽  
Paul C. Thande ◽  
Florence N. Wamwiri ◽  
...  
Keyword(s):  
Survival Time ◽  
Trypanosoma Brucei ◽  
Acute Infection ◽  
Glossina Pallidipes ◽  
Trypanosoma Congolense ◽  
Tsetse Fly ◽  
Economic Losses ◽  
Entire Group ◽  
Tsetse Flies ◽  
African Countries

African animal trypanosomiasis causes significant economic losses in sub-Saharan African countries because of livestock mortalities and reduced productivity. Trypanosomes, the causative agents, are transmitted by tsetse flies (Glossina spp.). In the current study, we compared and contrasted the virulence characteristics of five Trypanosoma congolense and Trypanosoma brucei isolates using groups of Swiss white mice (n = 6). We further determined the vectorial capacity of Glossina pallidipes, for each of the trypanosome isolates. Results showed that the overall pre-patent (PP) periods were 8.4 ± 0.9 (range, 4–11) and 4.5 ± 0.2 (range, 4–6) for T. congolense and T. brucei isolates, respectively (p < 0.01). Despite the longer mean PP, T. congolense–infected mice exhibited a significantly (p < 0.05) shorter survival time than T. brucei–infected mice, indicating greater virulence. Differences were also noted among the individual isolates with T. congolense KETRI 2909 causing the most acute infection of the entire group with a mean ± standard error survival time of 9 ± 2.1 days. Survival time of infected tsetse flies and the proportion with mature infections at 30 days post-exposure to the infective blood meals varied among isolates, with subacute infection–causing T. congolense EATRO 1829 and chronic infection–causing T. brucei EATRO 2267 isolates showing the highest mature infection rates of 38.5% and 23.1%, respectively. Therefore, our study provides further evidence of occurrence of differences in virulence and transmissibility of eastern African trypanosome strains and has identified two, T. congolense EATRO 1829 and T. brucei EATRO 2267, as suitable for tsetse infectivity and transmissibility experiments.

scholarly journals History of Sleeping Sickness in East Africa

1999 ◽  
Vol 12 (1) ◽  
pp. 112-125 ◽  
Author(s):  
Geoff Hide
Keyword(s):  
East Africa ◽  
Molecular Data ◽  
Sleeping Sickness ◽  
Tsetse Fly ◽  
Tsetse Flies ◽  
Agricultural Practice ◽  
Molecular Approaches ◽  
History Of ◽  
The Stability ◽  
The Right

SUMMARY The history of human sleeping sickness in East Africa is characterized by the appearance of disease epidemics interspersed by long periods of endemicity. Despite the presence of the tsetse fly in large areas of East Africa, these epidemics tend to occur multiply in specific regions or foci rather than spreading over vast areas. Many theories have been proposed to explain this phenomenon, but recent molecular approaches and detailed analyses of epidemics have highlighted the stability of human-infective trypanosome strains within these foci. The new molecular data, taken alongside the history and biology of human sleeping sickness, are beginning to highlight the important factors involved in the generation of epidemics. Specific, human-infective trypanosome strains may be associated with each focus, which, in the presence of the right conditions, can be responsible for the generation of an epidemic. Changes in agricultural practice, favoring the presence of tsetse flies, and the important contribution of domestic animals as a reservoir for the parasite are key factors in the maintenance of such epidemics. This review examines the contribution of molecular and genetic data to our understanding of the epidemiology and history of human sleeping sickness in East Africa.

Human African trypanosomiasis

2010 ◽  
pp. 1119-1127
Author(s):  
August Stich
Keyword(s):  
West Africa ◽  
East Africa ◽  
Trypanosoma Brucei ◽  
Human African Trypanosomiasis ◽  
Protozoan Parasite ◽  
Sleeping Sickness ◽  
Tsetse Flies ◽  
African Trypanosomiasis ◽  
Tropical Africa

Human African trypanosomiasis (HAT, sleeping sickness) is caused by two subspecies of the protozoan parasite Trypanosoma brucei: T. b. rhodesiense is prevalent in East Africa among many wild and domestic mammals; T. b. gambiense causes an anthroponosis in Central and West Africa. The disease is restricted to tropical Africa where it is transmitted by the bite of infected tsetse flies (...

scholarly journals A global sensitivity analysis for African sleeping sickness

Parasitology ◽  
2010 ◽  
Vol 138 (4) ◽  
pp. 516-526 ◽  
Author(s):  
STEPHEN DAVIS ◽  
SERAP AKSOY ◽  
ALISON GALVANI
Keyword(s):  
Trypanosoma Brucei ◽  
Control Strategies ◽  
Sleeping Sickness ◽  
Sensitivity Analyses ◽  
Tsetse Flies ◽  
East African ◽  
African Sleeping Sickness ◽  
Regular Treatment ◽  
Global Sensitivity ◽  
Parameter Ranges

SUMMARYAfrican sleeping sickness is a parasitic disease transmitted through the bites of tsetse flies of the genus Glossina. We constructed mechanistic models for the basic reproduction number, R0, of Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, respectively the causative agents of West and East African human sleeping sickness. We present global sensitivity analyses of these models that rank the importance of the biological parameters that may explain variation in R0, using parameter ranges based on literature, field data and expertize out of Uganda. For West African sleeping sickness, our results indicate that the proportion of bloodmeals taken from humans by Glossina fuscipes fuscipes is the most important factor, suggesting that differences in the exposure of humans to tsetse are fundamental to the distribution of T. b. gambiense. The second ranked parameter for T. b. gambiense and the highest ranked for T. b. rhodesiense was the proportion of Glossina refractory to infection. This finding underlines the possible implications of recent work showing that nutritionally stressed tsetse are more susceptible to trypanosome infection, and provides broad support for control strategies in development that are aimed at increasing refractoriness in tsetse flies. We note though that for T. b. rhodesiense the population parameters for tsetse – species composition, survival and abundance – were ranked almost as highly as the proportion refractory, and that the model assumed regular treatment of livestock with trypanocides as an established practice in the areas of Uganda experiencing East African sleeping sickness.

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