scholarly journals Tsetse Fly Saliva Accelerates the Onset of Trypanosoma brucei Infection in a Mouse Model Associated with a Reduced Host Inflammatory Response

2006 ◽  
Vol 74 (11) ◽  
pp. 6324-6330 ◽  
Author(s):  
Guy Caljon ◽  
Jan Van Den Abbeele ◽  
Benoît Stijlemans ◽  
Marc Coosemans ◽  
Patrick De Baetselier ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Inflammatory Responses ◽  
Blood Feeding ◽  
Immunoglobulin M ◽  
Tsetse Fly ◽  
Surface Glycoprotein ◽  
Tsetse Flies ◽  
Feeding Site ◽  
African Trypanosomes ◽  
Cytokine Tumor Necrosis Factor

ABSTRACT Tsetse flies (Glossina sp.) are the vectors that transmit African trypanosomes, protozoan parasites that cause human sleeping sickness and veterinary infections in the African continent. These blood-feeding dipteran insects deposit saliva at the feeding site that enables the blood-feeding process. Here we demonstrate that tsetse fly saliva also accelerates the onset of a Trypanosoma brucei infection. This effect was associated with a reduced inflammatory reaction at the site of infection initiation (reflected by a decrease of interleukin-6 [IL-6] and IL-12 mRNA) as well as lower serum concentrations of the trypanocidal cytokine tumor necrosis factor. Variant-specific surface glycoprotein-specific antibody isotypes immunoglobulin M (IgM) and IgG2a, implicated in trypanosome clearance, were not suppressed. We propose that tsetse fly saliva accelerates the onset of trypanosome infection by inhibiting local and systemic inflammatory responses involved in parasite control.

scholarly journals Expression site attenuation mechanistically links antigenic variation and development in Trypanosoma brucei

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Christopher Batram ◽  
Nicola G Jones ◽  
Christian J Janzen ◽  
Sebastian M Markert ◽  
Markus Engstler
Keyword(s):  
Trypanosoma Brucei ◽  
Histone Methylation ◽  
Antigenic Variation ◽  
Tsetse Fly ◽  
Developmental Competence ◽  
Surface Glycoprotein ◽  
G1 Phase ◽  
African Trypanosomes ◽  
Developmental Progression ◽  
Expression Site

We have discovered a new mechanism of monoallelic gene expression that links antigenic variation, cell cycle, and development in the model parasite Trypanosoma brucei. African trypanosomes possess hundreds of variant surface glycoprotein (VSG) genes, but only one is expressed from a telomeric expression site (ES) at any given time. We found that the expression of a second VSG alone is sufficient to silence the active VSG gene and directionally attenuate the ES by disruptor of telomeric silencing-1B (DOT1B)-mediated histone methylation. Three conserved expression-site-associated genes (ESAGs) appear to serve as signal for ES attenuation. Their depletion causes G1-phase dormancy and reversible initiation of the slender-to-stumpy differentiation pathway. ES-attenuated slender bloodstream trypanosomes gain full developmental competence for transformation to the tsetse fly stage. This surprising connection between antigenic variation and developmental progression provides an unexpected point of attack against the deadly sleeping sickness.

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.

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 Essential Roles for GPI-anchored Proteins in African Trypanosomes Revealed Using Mutants Deficient in GPI8

2003 ◽  
Vol 14 (3) ◽  
pp. 1182-1194 ◽  
Author(s):  
Simon Lillico ◽  
Mark C. Field ◽  
Pat Blundell ◽  
Graham H. Coombs ◽  
Jeremy C. Mottram
Keyword(s):  
Trypanosoma Brucei ◽  
Cell Cycle Progression ◽  
Tsetse Fly ◽  
Bloodstream Form ◽  
Surface Glycoprotein ◽  
Surface Coat ◽  
Immune Challenge ◽  
Gene Encoding ◽  
Cycle Progression ◽  
African Trypanosomes

The survival of Trypanosoma brucei, the causative agent of Sleeping Sickness and Nagana, is facilitated by the expression of a dense surface coat of glycosylphosphatidylinositol (GPI)-anchored proteins in both its mammalian and tsetse fly hosts. We have characterized T. brucei GPI8, the gene encoding the catalytic subunit of the GPI:protein transamidase complex that adds preformed GPI anchors onto nascent polypeptides. Deletion ofGPI8 (to give Δgpi8) resulted in the absence of GPI-anchored proteins from the cell surface of procyclic form trypanosomes and accumulation of a pool of non–protein-linked GPI molecules, some of which are surface located. Procyclic Δgpi8, while viable in culture, were unable to establish infections in the tsetse midgut, confirming that GPI-anchored proteins are essential for insect-parasite interactions. Applying specific inducible GPI8 RNAi with bloodstream form parasites resulted in accumulation of unanchored variant surface glycoprotein and cell death with a defined multinuclear, multikinetoplast, and multiflagellar phenotype indicative of a block in cytokinesis. These data show that GPI-anchored proteins are essential for the viability of bloodstream form trypanosomes even in the absence of immune challenge and imply that GPI8 is important for proper cell cycle progression.

Trypanosoma brucei: posttranscriptional control of the variable surface glycoprotein gene expression site

1989 ◽  
Vol 9 (9) ◽  
pp. 4018-4021
Author(s):  
E Pays ◽  
H Coquelet ◽  
A Pays ◽  
P Tebabi ◽  
M Steinert
Keyword(s):  
Gene Expression ◽  
Trypanosoma Brucei ◽  
Transcription Initiation ◽  
Tsetse Fly ◽  
Surface Glycoprotein ◽  
Insect Vector ◽  
Variable Surface Glycoprotein ◽  
A Genome ◽  
Variable Surface ◽  
Expression Site

The arrest of variable surface glycoprotein (VSG) synthesis is one of the first events accompanying the differentiation of Trypanosoma brucei bloodstream forms into procyclic forms, which are characteristic of the insect vector. This is because of a very fast inhibition of VSG gene transcription which occurs as soon as the temperature is lowered. We report that this effect is probably not controlled at the level of transcription initiation, since the beginning of the VSG gene expression site, about 45 kilobases upstream from the antigen gene, remains transcribed in procyclic forms. The permanent activity of the promoter readily accounts for the systematic reappearance, upon return to the bloodstream form after cyclical transmission, of the antigen type present before passage to the tsetse fly. The abortive transcription of the VSG gene expression site appears linked to RNA processing abnormalities. Such posttranscriptional controls may allow the modulation of gene expression in a genome organized in large multigenic transcription units.

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 In Vitro Generation of Human High-Density-Lipoprotein-Resistant Trypanosoma brucei brucei

2006 ◽  
Vol 5 (8) ◽  
pp. 1276-1286 ◽  
Author(s):  
Sara D. Faulkner ◽  
Monika W. Oli ◽  
Rudo Kieft ◽  
Laura Cotlin ◽  
Justin Widener ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Trypanosoma Brucei ◽  
Density Lipoprotein ◽  
High Density ◽  
Surface Glycoprotein ◽  
Trypanosoma Brucei Brucei ◽  
African Trypanosomes ◽  
Expression Site ◽  
Human High Density Lipoprotein

ABSTRACT The host range of African trypanosomes is influenced by innate protective molecules in the blood of primates. A subfraction of human high-density lipoprotein (HDL) containing apolipoprotein A-I, apolipoprotein L-I, and haptoglobin-related protein is toxic to Trypanosoma brucei brucei but not the human sleeping sickness parasite Trypanosoma brucei rhodesiense. It is thought that T. b. rhodesiense evolved from a T. b. brucei-like ancestor and expresses a defense protein that ablates the antitrypanosomal activity of human HDL. To directly investigate this possibility, we developed an in vitro selection to generate human HDL-resistant T. b. brucei. Here we show that conversion of T. b. brucei from human HDL sensitive to resistant correlates with changes in the expression of the variant surface glycoprotein (VSG) and abolished uptake of the cytotoxic human HDLs. Complete transcriptome analysis of the HDL-susceptible and -resistant trypanosomes confirmed that VSG switching had occurred but failed to reveal the expression of other genes specifically associated with human HDL resistance, including the serum resistance-associated gene (SRA) of T. b. rhodesiense. In addition, we found that while the original active expression site was still utilized, expression of three expression site-associated genes (ESAG) was altered in the HDL-resistant trypanosomes. These findings demonstrate that resistance to human HDLs can be acquired by T. b. brucei.

scholarly journals Escaping the immune system by DNA repair and recombination in African trypanosomes

Open Biology ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 190182 ◽  
Author(s):  
Núria Sima ◽  
Emilia Jane McLaughlin ◽  
Sebastian Hutchinson ◽  
Lucy Glover
Keyword(s):  
Immune Response ◽  
Dna Repair ◽  
Trypanosoma Brucei ◽  
Antigenic Variation ◽  
Surface Glycoprotein ◽  
Variant Surface Glycoprotein ◽  
Surface Coat ◽  
African Trypanosomes ◽  
Active Expression ◽  
Expression Site

African trypanosomes escape the mammalian immune response by antigenic variation—the periodic exchange of one surface coat protein, in Trypanosoma brucei the variant surface glycoprotein (VSG), for an immunologically distinct one. VSG transcription is monoallelic, with only one VSG being expressed at a time from a specialized locus, known as an expression site. VSG switching is a predominantly recombination-driven process that allows VSG sequences to be recombined into the active expression site either replacing the currently active VSG or generating a ‘new’ VSG by segmental gene conversion. In this review, we describe what is known about the factors that influence this process, focusing specifically on DNA repair and recombination.

scholarly journals Interpreting Morphological Adaptations Associated with Viviparity in the Tsetse Fly Glossina morsitans (Westwood) by Three-Dimensional Analysis

Insects ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 651
Author(s):  
Geoffrey M Attardo ◽  
Nicole Tam ◽  
Dula Parkinson ◽  
Lindsey K Mack ◽  
Xavier J Zahnle ◽  
...  
Keyword(s):  
Dimensional Analysis ◽  
Three Dimensional ◽  
Blood Feeding ◽  
Structural Features ◽  
Tsetse Fly ◽  
Reproductive Capacity ◽  
Tsetse Flies ◽  
Sexual Competition ◽  
Morphological Adaptations ◽  
Microscopy Techniques

Tsetse flies (genus Glossina), the sole vectors of African trypanosomiasis, are distinct from most other insects, due to dramatic morphological and physiological adaptations required to support their unique biology. These adaptations are driven by demands associated with obligate hematophagy and viviparous reproduction. Obligate viviparity entails intrauterine larval development and the provision of maternal nutrients for the developing larvae. The reduced reproductive capacity/rate associated with this biology results in increased inter- and intra-sexual competition. Here, we use phase contrast microcomputed tomography (pcMicroCT) to analyze morphological adaptations associated with viviparous biology. These include (1) modifications facilitating abdominal distention required during blood feeding and pregnancy, (2) abdominal and uterine musculature adaptations for gestation and parturition of developed larvae, (3) reduced ovarian structure and capacity, (4) structural features of the male-derived spermatophore optimizing semen/sperm delivery and inhibition of insemination by competing males and (5) structural features of the milk gland facilitating nutrient incorporation and transfer into the uterus. Three-dimensional analysis of these features provides unprecedented opportunities for examination and discovery of internal morphological features not possible with traditional microscopy techniques and provides new opportunities for comparative morphological analyses over time and between species.

scholarly journals Prevalence of Cattle Trypanosomosis and Apparent Density of Its Fly Vectors in Bambasi District of Benishangul-Gumuz Regional State, Western Ethiopia

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Morka Amante ◽  
Hika Tesgera
Keyword(s):  
Trypanosoma Brucei ◽  
Body Condition ◽  
Apparent Density ◽  
Tsetse Fly ◽  
Meat Production ◽  
Tsetse Flies ◽  
Trypanosoma Vivax ◽  
Trypanosome Species ◽  
Cross Sectional ◽  
Significant Difference

Trypanosomosis is the most serious disease of cattle, which causes great socioeconomic losses in the country. Its socioeconomic impact is reflected on direct losses due to mortality, morbidity, and reduction in milk and meat production, abortion and stillbirth, and also costs associated with combat of the disease are direct losses. A cross-sectional study was carried out to assess the prevalence of cattle trypanosomosis, and the apparent density and distribution of its fly vectors in selected study areas. The methods employed during the study were buffy coat technique for parasitological study and deploying trap for the collection of tsetse flies. A total of 1512 flies were trapped, and among them, 1162 were tsetse flies while 350 were biting flies. Higher apparent density for tsetse fly (7.7 F/T/D) followed by Stomoxys (0.9 F/T/D), Tabanus (0.8 F/T/D), and Hematopota (0.6 F/T/D) was recorded. Out of 638 examined cattle, the overall prevalence of trypanosomosis in the study area was 9.1% (58/638). Out of positive cases, Trypanosoma congolense (7.7%) was the dominant trypanosome species followed by Trypanosoma vivax (0.9%), Trypanosoma brucei (0.2%), and mixed infection of Trypanosoma brucei and Trypanosoma vivax (0.3%). There was no a significant difference (p>0.05) in trypanosome infection between age, sex, and trypanosome species. The prevalence of trypanosomosis on the bases of body condition was 2.8% for poor, 5.5% for medium, and 0.8% for good body condition. The overall prevalence of anemia was (36.8%), and presence of anemia was higher in trypanosome positive animals (62.5%) than in negative animals (34.3%) which is statistically significant (p<0.05, CI = 1.794–5.471). The overall mean packed cell volume (PCV) value for examined animals was 25.84 ± 0.252SE. Mean (PCV) of parasitaemic cattle (9.1%) was significantly (p<0.05) lower than that of aparasitaemic cattle (90%). This survey showed that trypanosomosis is still a core problem for livestock production of the study area. Therefore, more attention should be given to the control of both the disease and its vectors.

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