Neutralization of individual variable antigen types in metacyclic populations of Trypanosoma brucei does not prevent their subsequent expression in mice

Parasitology ◽  
1985 ◽  
Vol 90 (1) ◽  
pp. 79-88 ◽  
Author(s):  
J. D. Barry ◽  
J. S. Crowe ◽  
K. Vickerman
Keyword(s):  
Salivary Glands ◽  
Trypanosoma Brucei ◽  
Bloodstream Infections ◽  
Visual Observation ◽  
Tsetse Fly ◽  
Mammalian Host ◽  
Characteristic Set ◽  
Specific Antibodies ◽  
Antigenic Composition ◽  
Variable Antigen

The Trypanosoma brucei metacyclic population in the salivary glands of the tsetse fly displays a characteristic set of variable antigen types (VATs) which represents only a restricted part of the parasite's total VAT repertoire. After introduction into the mammalian host by fly bite, the metacyclics transform into bloodstream forms which retain expression of the metacyclic VATs. Specific antibodies, both polyvalent and monoclonal, have been used to neutralize separately 4 individual VATs from metacyclic populations. Control experiments and visual observation confirmed lysis of each VAT. On injection of the surviving trypanosomes, after washing, into mice each neutralized VAT was nevertheless expressed within a few days. Simultaneous neutralization of 2 metacyclic VATs which usually switch to one another in bloodstream infections did not prevent expression of either on subsequent injection into mice. Expression of neutralized VATs was not influenced by the antigenic composition of the population originally ingested by the tsetse fly. Metacyclic forms and their immediate successors thus appear to switch rapidly to expression of other metacyclic VATs in bloodstream populations.

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.

Antigenic variation in its biological context

1984 ◽  
Vol 307 (1131) ◽  
pp. 27-40 ◽  
Keyword(s):  
Salivary Glands ◽  
Antigenic Variation ◽  
Tsetse Fly ◽  
Mammalian Host ◽  
Full Understanding ◽  
Anamnestic Response ◽  
Insect Midgut ◽  
The Relationship ◽  
Biological Context

The biology of antigenic variation is discussed, and the problems that must be solved to provide a full understanding of antigenic variation are considered. These are (i) the induction of v.s.g. synthesis in the salivary glands of the tsetse fly; (ii) the nature of the restriction on v.s.g. genes that allows only some of them to be expressed in the salivary glands; (iii) the nature of ‘predominance’ in v.s.g. expression in the mammalian host, and the mechanism by which it operates; (iv) the repression of v.s.g. synthesis in the insect midgut; (v) the anamnestic response that produces expression of the ingested variant in the first patent parasitaemia in the mammalian host; (vi) the mechanism by which only one v.s.g. gene at a time is expressed; (vii) the relationship if any ofv.s.g. structure to v.s.g.-associated differences in growth rate and host range; (viii) the role of v.s.g. release within the life cycle and to pathogenesis.

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.

Trypanosome sociology and antigenic variation

Parasitology ◽  
1989 ◽  
Vol 99 (S1) ◽  
pp. S37-S47 ◽  
Author(s):  
K. Vickerman
Keyword(s):  
Trypanosoma Brucei ◽  
Antigenic Variation ◽  
Growth Characteristics ◽  
Tsetse Fly ◽  
Antigenic Specificity ◽  
Surface Coat ◽  
Humoral Immune ◽  
Variable Antigen ◽  
Minority Variants ◽  
Stimulation Of

SUMMARYSurvival of the trypanosome (Trypanosoma brucei) population in the mammalian body depends upon paced stimulation of the host's humoral immune response by different antigenic variants and serial sacrifice of the dominant variant (homotype) so that minority variants (heterotypes) can continue the infection and each become a homotype in its turn. New variants are generated by a spontaneous switch in gene expression so that the trypanosome puts on a surface coat of a glycoprotein differing in antigenic specificity from its predecessor. Homotypes appear in a characteristic order for a given trypanosome clone but what determines this order and the pacing of homotype generation so that the trypanosome does not quickly exhaust its repertoire of variable antigens, is not clear. The tendency of some genes to be expressed more frequently than others may reflect the location within the genome and mode of expression of the genes concerned and may influence homotype succession. Differences in the doubling time of different variants or in the rate at which trypanosomes belonging to a particular variant differentiate into non-dividing (vector infective) stumpy forms have also been invoked to explain how a heterotype's growth characteristics may determine when it becomes a homotype. Recent estimations of the frequency of variable antigen switching in trypanosome populations after transmission through the tsetse fly vector, however, suggest a much higher figure (0·97–2·2 × 10−3switches per cell per generation) than that obtained for syringe-passed infections (10−5–10−7switches per cell per generation) and it seems probable that most of the variable antigen genes are expressed as minority variable antigen types very early in the infection. Instability of expression is a feature of trypanosome clones derived from infective tsetse salivary gland (metacyclic) trypanosomes and it is suggested that high switching rates in tsetse-transmitted infections may delay the growth of certain variants to homotype status until later in the infection.

High frequency of antigenic variation inTrypanosoma brucei rhodesienseinfections

Parasitology ◽  
1989 ◽  
Vol 99 (1) ◽  
pp. 67-75 ◽  
Author(s):  
C. M. R. Turner ◽  
J. D. Barry
Keyword(s):  
High Frequency ◽  
Antigenic Variation ◽  
Bloodstream Infections ◽  
Tsetse Fly ◽  
Cell Generation ◽  
Switching Rate ◽  
Parental Stock ◽  
Variable Antigen ◽  
Growth Chambers ◽  
Systemic Infections

SUMMARYRates at whichTrypanosoma bruceirhodesiense trypanosomes switch from expression of one variable antigen type (VAT) to that of another have been determined in cloned populations that have been recently tsetse-fly transmitted. Switching rates have been determined between several, specific pairs of VATs in each population. High rates of switching were observed in 2 cloned trypanosome lines, each derived from a separate cyclical transmission of the same parental stock and each expressing a different major VAT. Five estimates of the switching rate between one particular pair of VATs were consistently high (approximately 1 × 103switches/cell/generation). These high switching rates were similar both in bloodstream populations of mice and in populations confined to subcutaneously implanted growth chambers in mice, thus indicating that the interaction of the bloodstream population with other trypanosome populations in the lymphatics or extravascular sites in systemic infections did not influence the estimates of the rate of switching. Fourteen estimates were made of VAT-specific switching rates in bloodstream infections involving 8 combinations from among 6 VATs. Switching rate estimates were VAT-specific and showed considerable variation between different combinations of VATs — from 1.9 × 10−6to 6.9 × 10−3switches/cel/generation. The rates of switching to different metacyclic-VATs were, however, very similar. Summation of between 3 and 5 VAT-specific switching rate values in each of 4 experiments conducted in bloodstream infections has provided minimum estimates of the overall rate of antigenic variation: 2.0−9.3 × 10−3switches/cell/generation. These values are between 20 and 66000-fold higher than previously published estimates. It is likely that at least 1 in every 100 trypanosomes switches its VAT expression every generation.

Onset of expression of the variant surface glycoproteins of Trypanosoma brucei in the tsetse fly studied using immunoelectron microscopy

1987 ◽  
Vol 87 (2) ◽  
pp. 363-372 ◽  
Author(s):  
L. Tetley ◽  
C.M. Turner ◽  
J.D. Barry ◽  
J.S. Crowe ◽  
K. Vickerman
Keyword(s):  
Trypanosoma Brucei ◽  
Tsetse Fly ◽  
Surface Glycoprotein ◽  
Variant Surface Glycoprotein ◽  
Fixed Sequence ◽  
Individual Variant ◽  
Variable Antigen ◽  
Variant Surface Glycoproteins ◽  
Scanning Electron

The acquisition of the variant surface glycoprotein (variable antigen) coat by metacyclic stage Trypanosoma brucei in the salivary glands of the tsetse fly, Glossina morsitans, has been studied in situ by transmission and scanning electron microscopy using monoclonal antibodies raised against metacyclic variable antigen types and complexed with horseradish peroxidase or colloidal gold. The coat is acquired after binary fission has ceased but while the parasite is still attached to the gland epithelium, i.e. before the mature metacyclic is released into the gland lumen. The variable antigen type heterogeneity previously observed in discharged mature metacyclics is here demonstrated in the nascent (attached) metacyclic population. The variant surface glycoprotein genes are thus not expressed in a fixed sequence since different metacyclic variable antigen types are present ab initio. The distribution of immunogold-marked nascent metacyclics of a particular variable antigen type, as shown by quadrat analysis of a scanning electron micrograph montage of the infected salivary gland epithelium, conforms to a Poisson series. This provides evidence that individual variant surface glycoprotein genes are stochastically activated and suggests that selective activation occurs after trypanosome division has ceased.

Antigenic variation in cyclically transmitted Trypanosoma brucei. Variable antigen type composition of metacyclic trypanosome populations from the salivary glands of Glossina morsitans

Parasitology ◽  
1981 ◽  
Vol 83 (3) ◽  
pp. 595-607 ◽  
Author(s):  
S. L. Hajduk ◽  
Cathy R. Cameron ◽  
J. D. Barry ◽  
K. Vickerman
Keyword(s):  
Salivary Glands ◽  
Trypanosoma Brucei ◽  
Indirect Immunofluorescence ◽  
Antigenic Variation ◽  
Tsetse Flies ◽  
Glossina Morsitans ◽  
Type Composition ◽  
Variable Antigen ◽  
Monospecific Antisera

SUMMARYTsetse flies (Glossina morsitans) were fed on the blood of mice containing any one of 5 variable antigen types (VATs) of Trypanosoma brucei AnTAR 1 serodeme. The VATs of the metacyclic trypanosomes subsequently detected in the flies' saliva probes were investigated using monospecific antisera to AnTAR 1 VATs in indirect immunofluorescence and trypanolysis reactions; these sera included 3 raised against AnTats 1.6, 1.30 and 1.45, previously identified as components of the metacyclic population (M-VATs), and against the 5 VATs originally ingested by the flies. The percentage of metacyclics reacting with a particular M-VAT antiserum remained more or less constant (AnTat 1.6, 6·0–8·3%; AnTat 1.30, 13·7–18·2%; AnTat 1.45, 2·0–8·0%), regardless of the age of the fly or the ingested VAT. As these 3 VATs accounted for no more than 30% of the metacyclic population, the existence of at least one more VAT is envisaged. The ingested VAT could not be detected among the AnTAR 1 metacyclic trypanosomes.

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 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.

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