The Cytological Events and Molecular Control of Life Cycle Development of Trypanosoma brucei in the Mammalian Bloodstream

Silvester, Eleanor; McWilliam, K. R.; Matthews, Keith R.

doi:10.3390/pathogens6030029

Cited by 63 publications

(64 citation statements)

References 117 publications

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“…Because these studies used lab-adapted monomorphic BF parasites that are only partially able to respond to authentic environment cues that are known to trigger pleomorphic parasites to differentiate (51,52), it is possible that these responses reflect unique behaviors of laboratory strains.…”

Section: Discussionmentioning

confidence: 99%

Identification of a post-transcriptional regulatory element that responds to glucose in the African trypanosome

Qiu

Shankar

Noorai

et al. 2018

Preprint

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The ability to adapt to varying nutrient availability in changing environments is critical for successful parasitism. The lifecycle stages of the African trypanosome, Trypanosoma brucei, that infect the host mammalian bloodstream utilize glucose exclusively for ATP production. The finding that trypanosomes also inhabit other tissues that frequently contain lower glucose concentrations suggests blood stage parasites may have to respond to a dynamic environment with changing nutrient availability in order to survive. However, little is known about how the parasites coordinate gene expression with nutrient availability. Through transcriptome analysis, we have found blood stage parasites deprived of glucose alter gene expression in a pattern similar to transcriptome changes triggered by other stresses. A surprisingly low concentration of glucose (<10 μM) was required to initiate the response. To further understand the dynamic regulation of gene expression that occurs in response to altered glucose availability in the environment, we have interrogated the 3'UTR of cytochrome c oxidase subunit VI, a known lifecycle stage regulated gene, and have identified a stem-loop structure that confers glucose-responsive regulation at the translational level.

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Section: Discussionmentioning

confidence: 99%

Identification of a post-transcriptional regulatory element that responds to glucose in the African trypanosome

Qiu

Shankar

Noorai

et al. 2018

Preprint

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“…The difference observed during the first parasitaemia peak may be attributed to the morphology of the infecting trypanosomes. At 21 DPI, BSF trypanosomes were represented by intermediate and short stumpy (SS) forms, which are non-proliferating and adapted to tsetse infection [31,32]. In contrast, CNS derived trypanosomes were long and slender as was also reported by Wolburg, [33].…”

Section: Discussionmentioning

confidence: 51%

Phenotypic characteristics distinguishing bloodstream form and central nervous form of Trypanosoma brucei rhodesiense.

Ndung'u¹,

Ga²,

Jk³

et al. 2020

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Background: Phenotypic and morphological characteristics distinguishing from bloodstream form (BSF) and central nervous system (CNS) of Trypanosoma brucei rhodesiense (Tbr) are poorly understood. Method: To identify these distinguishing characteristics, we separately infected four donor mice with each of five Tbr isolates (KETRI 2537/3537/2656/3459 and EATRO 2291). At 21 days post infection (DPI), donor mice were euthanized, BSF or CNS derived trypanosomes recovered and used for the following studies: 1) determination of morphological characteristics 2) pathogenicity studies using groups of 10 mice per isolate form. We then assessed differences in their lengths and morphology) and other characteristics including pre-patent period (PP), parasitaemia progression, packed cell volume (PCV), body weight, survival times, gross pathology, and histopathology. All analyses of data were conducted using GenStat, UK where p ⩽ 0.05 were considered statistically significant. Differences between and within the means were analyzed using one-way ANOVA. General Linear Model was used to analyze data on the length of the trypanosome. Survival data analysis was carried out employing the Kaplan–Meier method. Results: Morphologically, the CNS forms were predominantly long slender (LS) while BSF forms consisted of a mixture of short stumpy and intermediate forms. The mean length of CNS trypanosomes was 0.6 micrometer longer than their counterpart BSF derived trypanosomes. The PP was significantly (p<0.05) shorter and progression to peak parasitaemia faster (7 vs 9 days) in CNS than BSF derived trypanosomes. PCV declined by 21.6% and 26.9% in BSF and CNS infected mice respectively whereas non-infected control increased by 3.8% at 14 DPI. Body weight changes in BSF and CNS infected mice were (12.7% and 9.2% respectively) and significantly (p <0.05) lower than in non-infected control (27.6%) at 14 DPI. Gross pathology changes (splenomegaly and hepatomegaly) and histopathology changes were pronounced in mice infected with CNS relative to BSF trypanosome forms. Changes in histopathology included congestion, infiltration with inflammatory cells, hemolysis and necrosis, all indicators of differential virulence of the forms. Conclusion: Our study identified higher pathogenicity in CNS relative to BFS derived trypanosome forms in the mouse model. We also identified KETRI 2656 as a suitable isolate for acute menigo- encephalitic studies.

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“…When T. brucei, a unicellular kinetoplastid parasite, reaches a critical density in the 35 mammalian blood, a quorum-sensing mechanism is activated and the parasites differentiate 36 into quiescent, non-dividing stumpy forms (Vassella et al, 1997), limiting parasite population 37 size and extending host survival. The stumpy form also facilitates transmission to the tsetse fly 38 vector and development into insect procyclic forms (Silvester et al, 2017). In T. brucei, 39 parasite density is sensed via the stumpy induction factor (SIF) (Vassella et al, 1997) In eukaryotes, lncRNA gene abundance is comparable to that of protein coding genes 49 .…”

Section: Introduction 33 34mentioning

confidence: 99%

A long non-coding RNA controls parasite differentiation in African trypanosomes

Guegan

Bento

Neves

et al. 2020

Preprint

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16Trypanosoma brucei causes African sleeping sickness, a fatal human disease. Its differentiation 17 from replicative slender form into quiescent stumpy form promotes host survival and parasite 18 transmission. Long noncoding RNAs (lncRNAs) are known to regulate cell differentiation. To 19 determine whether lncRNAs are involved in parasite differentiation we used RNAseq to survey 20 the T. brucei lncRNA gene repertoire, identifying 1,428 previously uncharacterized lncRNA 21 genes. We analysed grumpy, a lncRNA located immediately upstream of an RNA-binding 22 protein that is a key differentiation regulator. Grumpy over-expression resulted in premature 23 parasite differentiation into the quiescent stumpy form, and subsequent impairment of in vivo 24 infection, decreasing parasite load in the mammalian host, and increasing host survival. Our 25 analyses suggest Grumpy is one of many lncRNA that modulate parasite-host interactions, and 26 lncRNA roles in cell differentiation are probably commonplace in T. brucei. 27 Keywords: 28Trypanosoma brucei, sleeping sickness, parasite, long non-coding RNAs, differentiation, 29 stumpy forms. 30 31 32

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The Cytological Events and Molecular Control of Life Cycle Development of Trypanosoma brucei in the Mammalian Bloodstream

Cited by 63 publications

References 117 publications

Identification of a post-transcriptional regulatory element that responds to glucose in the African trypanosome

Identification of a post-transcriptional regulatory element that responds to glucose in the African trypanosome

Phenotypic characteristics distinguishing bloodstream form and central nervous form of Trypanosoma brucei rhodesiense.

A long non-coding RNA controls parasite differentiation in African trypanosomes

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