Through the dark continent: African trypanosome development in the tsetse fly

Rotureau, Brice; Abbeele, Jan Van Den

doi:10.3389/fcimb.2013.00053

Cited by 115 publications

(116 citation statements)

References 39 publications

(51 reference statements)

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“…T. vivax, for example, which develops only in the fly mouthparts and foregut (62), has 14 AC genes (15). In comparison, development of T. congolense and T. brucei occurs not only in the mouthparts and foregut but also the midgut, with T. brucei additionally advancing through the salivary glands (62). Correspondingly, T. congolense and T. brucei have a larger cohort of AC genes, with approximately 45 and 65 chromosome-internal AC genes, respectively (15).…”

Section: Discussionmentioning

confidence: 99%

Insect Stage-Specific Receptor Adenylate Cyclases Are Localized to Distinct Subdomains of the Trypanosoma brucei Flagellar Membrane

et al. 2014

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cIncreasing evidence indicates that the Trypanosoma brucei flagellum (synonymous with cilium) plays important roles in hostparasite interactions. Several studies have identified virulence factors and signaling proteins in the flagellar membrane of bloodstream-stage T. brucei, but less is known about flagellar membrane proteins in procyclic, insect-stage parasites. Here we report on the identification of several receptor-type flagellar adenylate cyclases (ACs) that are specifically upregulated in procyclic T. brucei parasites. Identification of insect stage-specific ACs is novel, as previously studied ACs were constitutively expressed or confined to bloodstream-stage parasites. We show that procyclic stage-specific ACs are glycosylated, surface-exposed proteins that dimerize and possess catalytic activity. We used gene-specific tags to examine the distribution of individual AC isoforms. All ACs examined localized to the flagellum. Notably, however, while some ACs were distributed along the length of the flagellum, others specifically localized to the flagellum tip. These are the first transmembrane domain proteins to be localized specifically at the flagellum tip in T. brucei, emphasizing that the flagellum membrane is organized into specific subdomains. Deletion analysis reveals that C-terminal sequences are critical for targeting ACs to the flagellum, and sequence comparisons suggest that differential subflagellar localization might be specified by isoform-specific C termini. Our combined results suggest insect stage-specific roles for a subset of flagellar adenylate cyclases and support a microdomain model for flagellar cyclic AMP (cAMP) signaling in T. brucei. In this model, cAMP production is compartmentalized through differential localization of individual ACs, thereby allowing diverse cellular responses to be controlled by a common signaling molecule.

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Section: Discussionmentioning

confidence: 99%

Insect Stage-Specific Receptor Adenylate Cyclases Are Localized to Distinct Subdomains of the Trypanosoma brucei Flagellar Membrane

et al. 2014

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“…Some species of tsetse are refractory to infection by specific species of trypanosome and even when they are susceptible, the population of parasites in the midgut can be reduced making unsustainable the infection at this point 21,23,24. However some of the trypomastigote forms in the insect’s midgut may arrive to differentiate into procyclic forms, which replicate in situ and cross the peritrophic membrane to reach the proventriculus, where they becomes mesocyclic trypomastigotes and later epimastigote forms 17–19,22,23. Then, they migrate via the esophagus, proboscis, and hypopharynx to the salivary gland, where they are able to multiply and some of them can transform into infectious metacyclic forms 17–19,23.…”

Section: Transmission Cyclementioning

confidence: 99%

Epidemiology of human African trypanosomiasis

Franco¹,

Simarro²,

Diarra³

et al. 2014

CLEP

237

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Human African trypanosomiasis (HAT), or sleeping sickness, is caused by Trypanosoma brucei gambiense, which is a chronic form of the disease present in western and central Africa, and by Trypanosoma brucei rhodesiense, which is an acute disease located in eastern and southern Africa. The rhodesiense form is a zoonosis, with the occasional infection of humans, but in the gambiense form, the human being is regarded as the main reservoir that plays a key role in the transmission cycle of the disease. The gambiense form currently assumes that 98% of the cases are declared; the Democratic Republic of the Congo is the most affected country, with more than 75% of the gambiense cases declared. The epidemiology of the disease is mediated by the interaction of the parasite (trypanosome) with the vectors (tsetse flies), as well as with the human and animal hosts within a particular environment. Related to these interactions, the disease is confined in spatially limited areas called “foci”, which are located in Sub-Saharan Africa, mainly in remote rural areas. The risk of contracting HAT is, therefore, determined by the possibility of contact of a human being with an infected tsetse fly. Epidemics of HAT were described at the beginning of the 20th century; intensive activities have been set up to confront the disease, and it was under control in the 1960s, with fewer than 5,000 cases reported in the whole continent. The disease resurged at the end of the 1990s, but renewed efforts from endemic countries, cooperation agencies, and nongovernmental organizations led by the World Health Organization succeeded to raise awareness and resources, while reinforcing national programs, reversing the trend of the cases reported, and bringing the disease under control again. In this context, sustainable elimination of the gambiense HAT, defined as the interruption of the transmission of the disease, was considered as a feasible target for 2030. Since rhodesiense HAT is a zoonosis, where the animal reservoir plays a key role, the interruption of the disease’s transmission is not deemed feasible.

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“…It is exclusively transmitted by the bite of tsetse flies where its complex development involves several strictly organized differentiation and migration steps in distinct organs [1]. Although trypanosomes are protists, they can exhibit community behaviours as reported in the mammalian bloodstream, where the proliferative slender cells can trigger their differentiation into the tsetse-adapted stumpy form upon production of a 'stumpy induction factor' once they have reached a threshold density (as reviewed in [2]).…”

mentioning

confidence: 99%

“…Although trypanosomes are protists, they can exhibit community behaviours as reported in the mammalian bloodstream, where the proliferative slender cells can trigger their differentiation into the tsetse-adapted stumpy form upon production of a 'stumpy induction factor' once they have reached a threshold density (as reviewed in [2]). The existence of collective or social behaviour could also be considered when trypanosomes develop in the insect vector where they are subjected to drastic microenvironmental changes along the digestive tract, marked by high variations in population density and by migration steps from one tissue to another (reviewed in [1]). …”

mentioning

confidence: 99%