scholarly journals Positional dynamics and glycosomal recruitment of developmental regulators during trypanosome differentiation

2019 ◽  
Author(s):  
Balázs Szöőr ◽  
Dorina V. Simon ◽  
Federico Rojas ◽  
Julie Young ◽  
Derrick R. Robinson ◽  
...  
Keyword(s):  
Life Cycle ◽  
Tyrosine Phosphatase ◽  
Sub Saharan Africa ◽  
Metabolic Adaptation ◽  
Tsetse Flies ◽  
African Trypanosomes ◽  
Signalling Molecules ◽  
Life Cycle Stages ◽  
Sub Saharan ◽  
And Function

AbstractGlycosomes are peroxisome-related organelles that compartmentalise the glycolytic enzymes in kinetoplastid parasites. These organelles are developmentally regulated in their number and composition, allowing metabolic adaptation to the parasite’s needs in the blood of mammalian hosts or within their arthropod vector. A protein phosphatase cascade regulates differentiation between parasite developmental forms, comprising a tyrosine phosphatase, TbPTP1, that dephosphorylates and inhibits a serine threonine phosphatase TbPIP39 that promotes differentiation. When TbPTP1 is inactivated, TbPIP39 is activated and during differentiation becomes located in glycosomes. Here we have tracked TbPIP39 recruitment to glycosomes during differentiation from bloodstream stumpy forms to procyclic forms. Detailed microscopy and live cell imaging during the synchronous transition between life cycle stages revealed that in stumpy forms, TbPIP39 is located at a periflagellar pocket site closely associated with TbVAP, that defines the flagellar pocket endoplasmic reticulum. TbPTP1 is also located at the same site in stumpy forms, as is REG9.1, a regulator of stumpy-enriched mRNAs. This site provides a molecular node for the interaction between TbPTP1 and TbPIP39. Within 30 minutes of the initiation of differentiation TbPIP39 relocates to glycosomes whereas TbPTP1 disperses to the cytosol. Overall, the study identifies a ‘stumpy regulatory nexus’ (STuRN) that co-ordinates the molecular components of life cycle signalling and glycosomal development during transmission ofTrypanosoma brucei.ImportanceAfrican trypanosomes are parasites of sub-Saharan Africa responsible for both human and animal disease. The parasites are transmitted by tsetse flies and completion of their life cycle involves progression through several development steps. The initiation of differentiation between blood and tsetse forms is signalled by a phosphatase cascade, ultimately trafficked into peroxisome-related organelles called glycosomes that are unique to this group of organisms. Glycosomes undergo substantial remodelling of their composition and function during the differentiation step but how this is regulated is not understood. Here we identify a cytological site where the signalling molecules controlling differentiation converge before the dispersal of one of them into glycosomes. This coincides with a specialised ER site that may contribute to glycosome developmental biogenesis or regeneration. In combination, the study provides the first insight into the spatial co-ordination of signalling pathway components in trypanosomes as they undergo cell-type differentiation.

scholarly journals Positional Dynamics and Glycosomal Recruitment of Developmental Regulators during Trypanosome Differentiation

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Balázs Szöőr ◽  
Dorina V. Simon ◽  
Federico Rojas ◽  
Julie Young ◽  
Derrick R. Robinson ◽  
...  
Keyword(s):  
Life Cycle ◽  
Trypanosoma Brucei ◽  
Tyrosine Phosphatase ◽  
Tsetse Fly ◽  
Sub Saharan Africa ◽  
Metabolic Adaptation ◽  
Tsetse Flies ◽  
Content Type ◽  
African Trypanosomes ◽  
Sub Saharan

ABSTRACT Glycosomes are peroxisome-related organelles that compartmentalize the glycolytic enzymes in kinetoplastid parasites. These organelles are developmentally regulated in their number and composition, allowing metabolic adaptation to the parasite’s needs in the blood of mammalian hosts or within their arthropod vector. A protein phosphatase cascade regulates differentiation between parasite developmental forms, comprising a tyrosine phosphatase, Trypanosoma brucei PTP1 (TbPTP1), which dephosphorylates and inhibits a serine threonine phosphatase, TbPIP39, which promotes differentiation. When TbPTP1 is inactivated, TbPIP39 is activated and during differentiation becomes located in glycosomes. Here we have tracked TbPIP39 recruitment to glycosomes during differentiation from bloodstream “stumpy” forms to procyclic forms. Detailed microscopy and live-cell imaging during the synchronous transition between life cycle stages revealed that in stumpy forms, TbPIP39 is located at a periflagellar pocket site closely associated with TbVAP, which defines the flagellar pocket endoplasmic reticulum. TbPTP1 is also located at the same site in stumpy forms, as is REG9.1, a regulator of stumpy-enriched mRNAs. This site provides a molecular node for the interaction between TbPTP1 and TbPIP39. Within 30 min of the initiation of differentiation, TbPIP39 relocates to glycosomes, whereas TbPTP1 disperses to the cytosol. Overall, the study identifies a “stumpy regulatory nexus” (STuRN) that coordinates the molecular components of life cycle signaling and glycosomal development during transmission of Trypanosoma brucei. IMPORTANCE African trypanosomes are parasites of sub-Saharan Africa responsible for both human and animal disease. The parasites are transmitted by tsetse flies, and completion of their life cycle involves progression through several development steps. The initiation of differentiation between blood and tsetse fly forms is signaled by a phosphatase cascade, ultimately trafficked into peroxisome-related organelles called glycosomes that are unique to this group of organisms. Glycosomes undergo substantial remodeling of their composition and function during the differentiation step, but how this is regulated is not understood. Here we identify a cytological site where the signaling molecules controlling differentiation converge before the dispersal of one of them into glycosomes. In combination, the study provides the first insight into the spatial coordination of signaling pathway components in trypanosomes as they undergo cell-type differentiation.

African trypanosomes: the genome and adaptations for immune evasion

2011 ◽  
Vol 51 ◽  
pp. 47-62 ◽  
Author(s):  
Gloria Rudenko
Keyword(s):  
Immune Evasion ◽  
Cell Biology ◽  
Antigenic Variation ◽  
Critical Role ◽  
Sub Saharan Africa ◽  
Surface Glycoprotein ◽  
Tsetse Flies ◽  
African Trypanosomes ◽  
Genes Encoding ◽  
Sub Saharan

The African trypanosome Trypanosoma brucei is a flagellated unicellular parasite transmitted by tsetse flies that causes African sleeping sickness in sub-Saharan Africa. Trypanosomes are highly adapted for life in the hostile environment of the mammalian bloodstream, and have various adaptations to their cell biology that facilitate immune evasion. These include a specialized morphology, with most nutrient uptake occurring in the privileged location of the flagellar pocket. In addition, trypanosomes show extremely high rates of recycling of a protective VSG (variant surface glycoprotein) coat, whereby host antibodies are stripped off of the VSG before it is re-used. VSG recycling therefore functions as a mechanism for cleaning the VSG coat, allowing trypanosomes to survive in low titres of anti-VSG antibodies. Lastly, T. brucei has developed an extremely sophisticated strategy of antigenic variation of its VSG coat allowing it to evade host antibodies. A single trypanosome has more than 1500 VSG genes, most of which are located in extensive silent arrays. Strikingly, most of these silent VSGs are pseudogenes, and we are still in the process of trying to understand how non-intact VSGs are recombined to produce genes encoding functional coats. Only one VSG is expressed at a time from one of approximately 15 telomeric VSG ES (expression site) transcription units. It is becoming increasingly clear that chromatin remodelling must play a critical role in ES control. Hopefully, a better understanding of these unique trypanosome adaptations will eventually allow us to disrupt their ability to multiply in the mammalian bloodstream.

scholarly journals Slippery customers: How African trypanosomes evade mammalian defences

2009 ◽  
Vol 31 (4) ◽  
pp. 8-11
Author(s):  
Mark Carrington
Keyword(s):  
Cell Biology ◽  
Sub Saharan Africa ◽  
Mammalian Host ◽  
Tsetse Flies ◽  
Insect Vector ◽  
African Trypanosomiasis ◽  
Long Distance ◽  
African Trypanosomes ◽  
Endemic Areas ◽  
Sub Saharan

African trypanosomes are excellent parasites and can maintain an infection of a large mammalian host for months or years. In endemic areas, Human African Trypanosomiasis, also called sleeping sickness, has been largely unaffected by the advent of modern medicine, and trypanosomiasis of domestic livestock is a major restraint on productivity in endemic areas and is arguably the major contributor to the institutionalized poverty in much of rural sub-Saharan Africa1,2. A simple way of visualizing the effect of the livestock disease is to compare maps showing the distribution of livestock (www.ilri.org/InfoServ/Webpub/Fulldocs/Mappoverty/index.htm) and tsetse flies, the insect vector (www.fao.org/ag/AGAinfo/programmes/en/paat/maps.html): the lack of overlap is remarkable. Tsetse flies are only present in sub-Saharan Africa, and this probably restricted the spread of African trypanosomiasis until historical times. Livestock infections are now present in much of South Asia and South America, a product of long distance trade and adaptation of the trypanosomes to mechanical transmission3. The majority of research is on Trypanosoma brucei as this includes the human infective subspecies. This article provides a description of progress in the understanding the molecular details of how the trypanosome interacts with the mammalian immune system and how these studies have extended beyond this to fundamental aspects of eukaryotic cell biology.

scholarly journals Unexpected plasticity in the life cycle of Trypanosoma brucei

2019 ◽  
Author(s):  
Sarah Schuster ◽  
Ines Subota ◽  
Jaime Lisack ◽  
Henriette Zimmermann ◽  
Christian Reuter ◽  
...  
Keyword(s):  
Life Cycle ◽  
Parasite Load ◽  
Tsetse Fly ◽  
Productive Infection ◽  
Complex Life Cycle ◽  
Tsetse Flies ◽  
Chronic Infections ◽  
African Trypanosomes ◽  
Life Cycle Stages ◽  
Shed Light

AbstractAfrican trypanosomes cause sleeping sickness in humans and nagana in cattle. These unicellular parasites are transmitted by the bloodsucking tsetse fly. In the mammalian host’s circulation, tissues, and interstitium, at least two main life cycle stages exist: slender and stumpy bloodstream stages. Proliferating slender stage cells differentiate into cell cycle-arrested stumpy stage cells at high population densities. This developmental stage transition occurs in response to the quorum sensing factor SIF (stumpy induction factor), and is thought to fulfil two main functions. First, it auto-regulates the parasite load in the host. Second, the stumpy stage is regarded as pre-adapted for tsetse fly infection and the only stage capable of successful vector transmission. Here, we show that proliferating slender stage trypanosomes are able to complete the complex life cycle in the fly as successfully as the stumpy stage, and that a single parasite is sufficient for productive infection. Our findings not only propose a revision to the traditional rigid view of the trypanosome life cycle, but also suggest a solution to a long-acknowledged paradox in the transmission event: parasitaemia in chronic infections is characteristically low, and so the probability of a tsetse ingesting a stumpy cell during a bloodmeal is also low. The finding that proliferating slender parasites are infective to tsetse flies helps shed light on this enigma.

scholarly journals Colonization of the tsetse fly midgut with commensal Enterobacter inhibits trypanosome infection establishment

2018 ◽  
Author(s):  
Brian L. Weiss ◽  
Michele A. Maltz ◽  
Aurélien Vigneron ◽  
Yineng Wu ◽  
Katharine Walter ◽  
...  
Keyword(s):  
Control Strategies ◽  
Vector Competence ◽  
Tsetse Fly ◽  
Sub Saharan Africa ◽  
Tsetse Flies ◽  
Wild Type ◽  
African Trypanosomes ◽  
Control Programs ◽  
Causative Agents ◽  
Sub Saharan

AbstractTsetse flies (Glossina spp.) vector pathogenic trypanosomes (Trypanosoma spp.) in sub-Saharan Africa. These parasites cause human and animal African trypanosomiases, which are debilitating diseases that inflict an enormous socio-economic burden on inhabitants of endemic regions. Current disease control strategies rely primarily on treating infected animals and reducing tsetse population densities. However, relevant programs are costly, labor intensive and difficult to sustain. As such, novel strategies aimed at reducing tsetse vector competence require development. Herein we investigated whether an Enterobacter bacterium (Esp_Z), which confers Anopheles gambiae with resistance to Plasmodium, is able to colonize tsetse and induce a trypanosome refractory phenotype in the fly. Esp_Z established stable infections in tsetse’s gut, and exhibited no adverse effect on the survival of individuals from either group. Flies with established Esp_Z infections in their gut were significantly more refractory to infection with two distinct trypanosome species (T. congolense, 6% infection; T. brucei, 32% infection) than were age-matched flies that did not house the exogenous bacterium (T. congolense, 36% infected; T. brucei, 70% infected). Additionally, 52% of Esp_Z colonized tsetse survived infection with entomopathogenic Serratia marcescens, compared with only 9% of their wild-type counterparts. These parasite and pathogen refractory phenotypes result from the fact that Esp_Z acidifies tsetse’s midgut environment, which inhibits trypanosome and Serratia growth and thus infection establishment. Finally, we determined that Esp_Z infection does not impact the fecundity of male or female tsetse, nor the ability of male flies to compete with their wild-type counterparts for mates. We propose that Esp_Z could be used as one component of an integrated strategy aimed at reducing the ability of tsetse to transmit pathogenic trypanosomes.Author SummaryTsetse flies transmit pathogenic African trypanosomes, which are the causative agents of socio-economically devastating human and animal African trypanosomiases. These diseases are currently controlled in large part by reducing the population size of tsetse vectors through the use of insecticides, traps and sterile insect technique. However, logistic and monetary hurdles often preclude the prolonged application of procedures necessary to maintain these control programs. Thus, novel strategies, including those aimed at sustainably reducing the ability of tsetse to transmit trypanosomes, are presently under development. Herein we stably colonize tsetse flies with a bacterium (Enterobacter sp. Z, Esp_Z) that acidifies their midgut, thus rendering the environment inhospitable to infection with two distinct, epidemiologically important trypanosome strains as well as an entomopathogenic bacteria. In addition to inducing a trypanosome refractory phenotype, colonization of tsetse with Esp_Z exerts only a modest fitness cost on the fly. Taken together, these findings suggest that Esp_Z could be applied to enhance the effectiveness of currently employed tsetse control programs.

scholarly journals Mitochondrial Processes during Early Development of Dictyostelium discoideum: From Bioenergetic to Proteomic Studies

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 638
Author(s):  
Monika Mazur ◽  
Daria Wojciechowska ◽  
Ewa Sitkiewicz ◽  
Agata Malinowska ◽  
Bianka Świderska ◽  
...  
Keyword(s):  
Life Cycle ◽  
Developmental Stages ◽  
Coupling Efficiency ◽  
Slime Mold ◽  
Intact Cells ◽  
Life Cycle Stages ◽  
Early Developmental Stages ◽  
Proteomic Study ◽  
And Function ◽  
Early Developmental

The slime mold Dictyostelium discoideum’s life cycle includes different unicellular and multicellular stages that provide a convenient model for research concerning intracellular and intercellular mechanisms influencing mitochondria’s structure and function. We aim to determine the differences between the mitochondria isolated from the slime mold regarding its early developmental stages induced by starvation, namely the unicellular (U), aggregation (A) and streams (S) stages, at the bioenergetic and proteome levels. We measured the oxygen consumption of intact cells using the Clarke electrode and observed a distinct decrease in mitochondrial coupling capacity for stage S cells and a decrease in mitochondrial coupling efficiency for stage A and S cells. We also found changes in spare respiratory capacity. We performed a wide comparative proteomic study. During the transition from the unicellular stage to the multicellular stage, important proteomic differences occurred in stages A and S relating to the proteins of the main mitochondrial functional groups, showing characteristic tendencies that could be associated with their ongoing adaptation to starvation following cell reprogramming during the switch to gluconeogenesis. We suggest that the main mitochondrial processes are downregulated during the early developmental stages, although this needs to be verified by extending analogous studies to the next slime mold life cycle stages.

Antioxidants promote establishment of trypanosome infections in tsetse

Parasitology ◽  
2007 ◽  
Vol 134 (6) ◽  
pp. 827-831 ◽  
Author(s):  
E. T. MacLEOD ◽  
I. MAUDLIN ◽  
A. C. DARBY ◽  
S. C. WELBURN
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Trypanosoma Brucei ◽  
Sub Saharan Africa ◽  
Tsetse Flies ◽  
Oxygen Species ◽  
Infection Rates ◽  
Trypanosoma Brucei Brucei ◽  
Sub Saharan ◽  
Cyclical Transmission

SUMMARYEfficient, cyclical transmission of trypanosomes through tsetse flies is central to maintenance of human sleeping sickness and nagana across sub-Saharan Africa. Infection rates in tsetse are normally very low as most parasites ingested with the fly bloodmeal die in the fly gut, displaying the characteristics of apoptotic cells. Here we show that a range of antioxidants (glutathione, cysteine, N-acetyl-cysteine, ascorbic acid and uric acid), when added to the insect bloodmeal, can dramatically inhibit cell death of Trypanosoma brucei brucei in tsetse. Both L- and D-cysteine invoked similar effects suggesting that inhibition of trypanosome death is not dependent on protein synthesis. The present work suggests that antioxidants reduce the midgut environment protecting trypanosomes from cell death induced by reactive oxygen species.

scholarly journals Glucose Signaling Is Important for Nutrient Adaptation during Differentiation of Pleomorphic African Trypanosomes

mSphere ◽  
2018 ◽  
Vol 3 (5) ◽  
Author(s):  
Yijian Qiu ◽  
Jillian E. Milanes ◽  
Jessica A. Jones ◽  
Rooksana E. Noorai ◽  
Vijay Shankar ◽  
...  
Keyword(s):  
Life Cycle ◽  
Glucose Sensing ◽  
Negative Regulator ◽  
Bloodstream Form ◽  
Tsetse Flies ◽  
Insect Vector ◽  
Rapid Reduction ◽  
African Trypanosomes ◽  
Procyclic Form ◽  
African Trypanosome

ABSTRACT The African trypanosome has evolved mechanisms to adapt to changes in nutrient availability that occur during its life cycle. During transition from mammalian blood to insect vector gut, parasites experience a rapid reduction in environmental glucose. Here we describe how pleomorphic parasites respond to glucose depletion with a focus on parasite changes in energy metabolism and growth. Long slender bloodstream form parasites were rapidly killed as glucose concentrations fell, while short stumpy bloodstream form parasites persisted to differentiate into the insect-stage procyclic form parasite. The rate of differentiation was lower than that triggered by other cues but reached physiological rates when combined with cold shock. Both differentiation and growth of resulting procyclic form parasites were inhibited by glucose and nonmetabolizable glucose analogs, and these parasites were found to have upregulated amino acid metabolic pathway component gene expression. In summary, glucose transitions from the primary metabolite of the blood-stage infection to a negative regulator of cell development and growth in the insect vector, suggesting that the hexose is not only a key metabolic agent but also an important signaling molecule. IMPORTANCE As the African trypanosome Trypanosoma brucei completes its life cycle, it encounters many different environments. Adaptation to these environments includes modulation of metabolic pathways to parallel the availability of nutrients. Here, we describe how the blood-dwelling life cycle stages of the African trypanosome, which consume glucose to meet their nutritional needs, respond differently to culture in the near absence of glucose. The proliferative long slender parasites rapidly die, while the nondividing short stumpy parasite remains viable and undergoes differentiation to the next life cycle stage, the procyclic form parasite. Interestingly, a sugar analog that cannot be used as an energy source inhibited the process. Furthermore, the growth of procyclic form parasite that resulted from the event was inhibited by glucose, a behavior that is similar to that of parasites isolated from tsetse flies. Our findings suggest that glucose sensing serves as an important modulator of nutrient adaptation in the parasite.

scholarly journals CONTINENTAL MUSICOLOGY: DECOLONISING THE MYTH OF A SINGULAR “AFRICAN MUSIC”

2018 ◽  
Vol 10 (4) ◽  
pp. 177-193
Author(s):  
Thomas Mathew Pooley
Keyword(s):  
Sub Saharan Africa ◽  
Power Dynamics ◽  
Musical Structure ◽  
African Music ◽  
Popular Imagination ◽  
Ideal Types ◽  
Musical Identity ◽  
The North ◽  
Sub Saharan ◽  
And Function

The musical identity of the African continent is sustained in the popular imagination by the idea of its unity. This identity emerges from a constellation of ideas about Africa’s distinctiveness constructed by generations of scholars who have diminished its diversity to substantiate the claim that shared principles of musical structure and function in sub-Saharan cultures can be read as ideal types for the continent as a whole. The idea of a singular “African music” is predicated on the notion that African “traditional” music of precolonial origin in sub-Saharan Africa possesses a set of distinctive features that are essential to its identity. Musical cultures as diverse as Aka, Ewe, Shona, Yoruba, and Zulu are subsumed within a singular frame of reference; others that do not possess these features are, by implication, excluded. To make sense of this myth of a singular “African music” we must reckon with the universalising impulse that sustains it. This means interrogating the discursive formations out of which it has been fashioned. Whose interests does it serve? Taking a decolonial perspective on the power dynamics that structure global south-north relations in the academy, this article points to the ways in which the north perpetuates its authority and dominance over the south by subsuming others within its cultural and intellectual ambit. Decolonising “African music” means dismantling the hegemony of “continental musicology” and the myth of a singular “African music” that is its creation.

Sign in / Sign up

Export Citation Format

Share Document