Proteomics and theTrypanosoma bruceicytoskeleton: advances and opportunities

Parasitology ◽  
2012 ◽  
Vol 139 (9) ◽  
pp. 1168-1177 ◽  
Author(s):  
NEIL PORTMAN ◽  
KEITH GULL
Keyword(s):  
Life Cycle ◽  
Trypanosoma Brucei ◽  
Cell Biology ◽  
Molecular Composition ◽  
Etiological Agent ◽  
Sub Saharan Africa ◽  
Parasitic Disease ◽  
Cell Cycles ◽  
Sub Saharan ◽  
High Level

SUMMARYTrypanosoma bruceiis the etiological agent of devastating parasitic disease in humans and livestock in sub-saharan Africa. The pathogenicity and growth of the parasite are intimately linked to its shape and form. This is in turn derived from a highly ordered microtubule cytoskeleton that forms a tightly arrayed cage directly beneath the pellicular membrane and numerous other cytoskeletal structures such as the flagellum. The parasite undergoes extreme changes in cellular morphology during its life cycle and cell cycles which require a high level of integration and coordination of cytoskeletal processes. In this review we will discuss the role that proteomics techniques have had in advancing our understanding of the molecular composition of the cytoskeleton and its functions. We then consider future opportunities for the application of these techniques in terms of addressing some of the unanswered questions of trypanosome cytoskeletal cell biology with particular focus on the differences in the composition and organisation of the cytoskeleton through the trypanosome life-cycle.

scholarly journals Mechanisms of Arsenical and Diamidine Uptake and Resistance in Trypanosoma brucei

2003 ◽  
Vol 2 (5) ◽  
pp. 1003-1008 ◽  
Author(s):  
Enock Matovu ◽  
Mhairi L. Stewart ◽  
Federico Geiser ◽  
Reto Brun ◽  
Pascal Mäser ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Drug Sensitivity ◽  
Sleeping Sickness ◽  
Drug Uptake ◽  
Sub Saharan Africa ◽  
Parental Line ◽  
Adenosine Transport ◽  
Sub Saharan ◽  
High Level

ABSTRACT Sleeping sickness, caused by Trypanosoma brucei spp., has become resurgent in sub-Saharan Africa. Moreover, there is an alarming increase in treatment failures with melarsoprol, the principal agent used against late-stage sleeping sickness. In T. brucei, the uptake of melarsoprol as well as diamidines is thought to be mediated by the P2 aminopurine transporter, and loss of P2 function has been implicated in resistance to these agents. The trypanosomal gene TbAT1 has been found to encode a P2-type transporter when expressed in yeast. Here we investigate the role of TbAT1 in drug uptake and drug resistance in T. brucei by genetic knockout of TbAT1. Tbat1-null trypanosomes were deficient in P2-type adenosine transport and lacked adenosine-sensitive transport of pentamidine and melaminophenyl arsenicals. However, the null mutants were only slightly resistant to melaminophenyl arsenicals and pentamidine, while resistance to other diamidines such as diminazene was more pronounced. Nevertheless, the reduction in drug sensitivity might be of clinical significance, since mice infected with tbat1-null trypanosomes could not be cured with 2 mg of melarsoprol/kg of body weight for four consecutive days, whereas mice infected with the parental line were all cured by using this protocol. Two additional pentamidine transporters, HAPT1 and LAPT1, were still present in the null mutant, and evidence is presented that HAPT1 may be responsible for the residual uptake of melaminophenyl arsenicals. High-level arsenical resistance therefore appears to involve the loss of more than one transporter.

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.

scholarly journals Mapping of affordability levels for photovoltaic-based electricity generation in the solar belt of sub-Saharan Africa, East Asia and South Asia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sándor Szabó ◽  
Irene Pinedo Pascua ◽  
Daniel Puig ◽  
Magda Moner-Girona ◽  
Mario Negre ◽  
...  
Keyword(s):  
East Asia ◽  
South Asia ◽  
Electricity Generation ◽  
Sub Saharan Africa ◽  
Solar Photovoltaic ◽  
Term Operation ◽  
Sub Saharan ◽  
High Level ◽  
Do So

AbstractLack of access to modern forms of energy hampers efforts to reduce poverty. The provision of electricity to off-grid communities is therefore a long-standing developmental goal. Yet, many off-grid electrification projects neglect mid- and long-term operation and maintenance costs. When this is the case, electricity services are unlikely to be affordable to the communities that are the project’s primary target. Here we show that, compared with diesel-powered electricity generation systems, solar photovoltaic systems are more affordable to no less than 36% of the unelectrified populations in East Asia, South Asia, and sub-Saharan Africa. We do so by developing geo-referenced estimates of affordability at a high level of resolution (1 km2). The analysis illustrates the differences in affordability that may be found at the subnational level, which underscores that electrification investments should be informed by subnational data.

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 Salivarian Trypanosomes Have Adopted Intricate Host-Pathogen Interaction Mechanisms that Ensure Survival in Plain Sight of the Adaptive Immune System

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 679
Author(s):  
Stefan Magez ◽  
Joar Esteban Pinto Torres ◽  
Seoyeon Oh ◽  
Magdalena Radwanska
Keyword(s):  
Immune System ◽  
Trypanosoma Brucei ◽  
Adaptive Immune System ◽  
Sub Saharan Africa ◽  
Survival Strategies ◽  
Mechanical Transmission ◽  
Sub Saharan ◽  
Animal Trypanosomiasis ◽  
Host Parasite ◽  
Treatment And Diagnosis

Salivarian trypanosomes are extracellular parasites affecting humans, livestock and game animals. Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense are human infective sub-species of T. brucei causing human African trypanosomiasis (HAT—sleeping sickness). The related T. b. brucei parasite lacks the resistance to survive in human serum, and only inflicts animal infections. Animal trypanosomiasis (AT) is not restricted to Africa, but is present on all continents. T. congolense and T. vivax are the most widespread pathogenic trypanosomes in sub-Saharan Africa. Through mechanical transmission, T. vivax has also been introduced into South America. T. evansi is a unique animal trypanosome that is found in vast territories around the world and can cause atypical human trypanosomiasis (aHT). All salivarian trypanosomes are well adapted to survival inside the host’s immune system. This is not a hostile environment for these parasites, but the place where they thrive. Here we provide an overview of the latest insights into the host-parasite interaction and the unique survival strategies that allow trypanosomes to outsmart the immune system. In addition, we review new developments in treatment and diagnosis as well as the issues that have hampered the development of field-applicable anti-trypanosome vaccines for the implementation of sustainable disease control.

Poverty prevalence and negative spillovers in Sub-Saharan Africa: a focus on extreme and multidimensional poverty in the region

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Olumide Olaoye ◽  
Cleopatra Oluseye Ibukun ◽  
Mustafa Razzak ◽  
Naftaly Mose
Keyword(s):  
Generalized Method Of Moments ◽  
Spillover Effect ◽  
Multidimensional Poverty ◽  
Sub Saharan Africa ◽  
Cross Sectional ◽  
Spatial Error ◽  
Content Type ◽  
The Sustainable Development ◽  
Sub Saharan ◽  
High Level

PurposeThe paper analyses the prevalence of extreme and multidimensional poverty in line with the sustainable development agenda. In addition, the paper examines the drivers of extreme poverty while accounting for the potential spillover effect of poverty in the region.Design/methodology/approachThe study adopts the pooled OLS with Discroll-Kraay robust standard errors to control for cross-sectional dependence. In addition, given the strong potential for endogeneity of poverty index, the authors also employ the generalized method of moments (GMM), which accounts for simultaneity and endogeneity problems, and the spatial error and lag models to control for all forms of spatial and temporal dependence since the factors that affect poverty disperse across borders.FindingsThe study finds that in addition to the traditional drivers of poverty (unemployment, low per capita GDP growth and public debt), poverty in Sub-Saharan Africa is a symptom of a deeper structural problem (lack of access to water and sanitation, high level of corruption and low level of financial development, and frequent economic busts). Likewise, the results from the spatial econometric specification show, consistently across all the specifications, that there is a substantial spillover effect of poverty across the region.Originality/valueThe main novelty of the paper is that the authors investigate the “economic shrinkage hypothesis,” and examined the potential negative spillover effect of poverty in the region.

Guinea worm disease (dracunculiasis)

2020 ◽  
pp. 1495-1500
Author(s):  
Richard Knight
Keyword(s):  
Life Cycle ◽  
Bacterial Infection ◽  
Clinical Presentation ◽  
Subcutaneous Tissue ◽  
Sub Saharan Africa ◽  
Prodromal Symptoms ◽  
Guinea Worm ◽  
Safe Water ◽  
Infective Larvae ◽  
Sub Saharan

Guinea worm disease (dracunculiasis)—now limited to sub-Saharan Africa—is caused by the nematode Dracunculus medinensis, whose life cycle involves aquatic copepod crustaceans. Humans are infected when they drink water containing infective larvae. Adult worms enter subcutaneous tissue and can reach a metre in length. Clinical presentation is usually with a skin blister, most often on the leg, sometimes preceded by allergic prodromal symptoms. Bacterial infection and local scarring with disability are common complications. Most patients in endemic areas recognize their condition, but irrigation of ulcers can reveal larvae. Treatment is by physical removal of the worm; anthelmintics have no role in management. Provision of safe water for drinking is the key to prevention. The disease is now nearing eradication.

scholarly journals Homozygosity for TYK2 P1104A underlies tuberculosis in about 1% of patients in a cohort of European ancestry

2019 ◽  
Vol 116 (21) ◽  
pp. 10430-10434 ◽  
Author(s):  
Gaspard Kerner ◽  
Noe Ramirez-Alejo ◽  
Yoann Seeleuthner ◽  
Rui Yang ◽  
Masato Ogishi ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Genetic Basis ◽  
Sub Saharan Africa ◽  
European Ancestry ◽  
Uk Biobank ◽  
The United Kingdom ◽  
The Common ◽  
Sub Saharan ◽  
The Uk ◽  
High Level

The human genetic basis of tuberculosis (TB) has long remained elusive. We recently reported a high level of enrichment in homozygosity for the common TYK2 P1104A variant in a heterogeneous cohort of patients with TB from non-European countries in which TB is endemic. This variant is homozygous in ∼1/600 Europeans and ∼1/5,000 people from other countries outside East Asia and sub-Saharan Africa. We report a study of this variant in the UK Biobank cohort. The frequency of P1104A homozygotes was much higher in patients with TB (6/620, 1%) than in controls (228/114,473, 0.2%), with an odds ratio (OR) adjusted for ancestry of 5.0 [95% confidence interval (CI): 1.96–10.31, P = 2 × 10−3]. Conversely, we did not observe enrichment for P1104A heterozygosity, or for TYK2 I684S or V362F homozygosity or heterozygosity. Moreover, it is unlikely that more than 10% of controls were infected with Mycobacterium tuberculosis, as 97% were of European genetic ancestry, born between 1939 and 1970, and resided in the United Kingdom. Had all of them been infected, the OR for developing TB upon infection would be higher. These findings suggest that homozygosity for TYK2 P1104A may account for ∼1% of TB cases in Europeans.

Assessing Assets Among Street-Connected Youth: New Angles With Participatory Methods in Tanzania

2019 ◽  
Vol 34 (5) ◽  
pp. 619-651
Author(s):  
Laura R. Johnson ◽  
Christopher F. Drescher ◽  
Sophia H. Assenga ◽  
Rachel J. Marsh
Keyword(s):  
Contextual Information ◽  
Research Process ◽  
Street Youth ◽  
Sub Saharan Africa ◽  
Participatory Methods ◽  
Multiple Perspectives ◽  
Use Of Time ◽  
Northern Tanzania ◽  
Sub Saharan ◽  
High Level

Street-connected adolescents in sub-Saharan Africa have been neglected in scholarly research. Extant literature is largely problem focused. This study describes strengths and assets among street-connected youth in Tanzania, using a participatory, mixed methods approach. Adolescents ( N = 38, 13-17 years) in a rehabilitation center for street youth in Northern Tanzania completed a Swahili version of the Developmental Assets Profile (DAP). They engaged in participatory activities designed to capture multiple perspectives and promote maximal engagement. A subsample of youth ( n = 8) took part in photovoice to elucidate contextual details. Although exploratory, we expected (a) participants would have lower scores on the external versus internal domain of the DAP; (b) qualitative methods would support the DAP and provide complementary, contextual information; and (c) participatory methods would be important for providing varied perspectives and engaging youth in the research process. Results revealed a moderately high level of assets, with strengths in constructive use of time and commitment to school. External assets were higher than internal assets; however, different assets were emphasized across different methods. Overall, results supported the DAP framework. The participatory approaches effectively engaged youth and illuminated the culture and context of their development.

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