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New discoveries in the transmission biology of sleeping sickness parasites: applying the basics.

MacGregor P, Matthews KR - J. Mol. Med. (2010)

Bottom Line: One developmental form, the bloodstream stumpy stage, plays an important role in infection dynamics and transmission of the parasite.These molecular advances now provide improved experimental tools for the study of stumpy formation and function within the mammalian bloodstream.Here, we shall discuss the recent advances that have been made and the prospects for future research now available.

View Article: PubMed Central - PubMed

Affiliation: Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Kings Buildings, West Mains Road, Edinburgh, EH9 3JT, UK.

ABSTRACT
The sleeping sickness parasite, Trypanosoma brucei, must differentiate in response to the changing environments that it encounters during its complex life cycle. One developmental form, the bloodstream stumpy stage, plays an important role in infection dynamics and transmission of the parasite. Recent advances have shed light on the molecular mechanisms by which these stumpy forms differentiate as they are transmitted from the mammalian host to the insect vector of sleeping sickness, tsetse flies. These molecular advances now provide improved experimental tools for the study of stumpy formation and function within the mammalian bloodstream. They also offer new routes to therapy via high-throughput screens for agents that accelerate parasite development. Here, we shall discuss the recent advances that have been made and the prospects for future research now available.

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Related in: MedlinePlus

A simplified depiction of the T. brucei life cycle. In the bloodstream of the mammalian host, slender forms proliferate. As density increases, the parasites produce stumpy induction factor (SIF) which induces differentiation of a proportion of slender forms to stumpy forms. Stumpy forms are pre-adapted to life in the tsetse vector: they are cell cycle-arrested and have elaborated mitochondrial activity. Upon uptake in a tsetse blood-meal, stumpy forms differentiate into the proliferative procyclic forms in response to cold shock and cis-aconitate or citrate (CCA) in the tsetse midgut. Other signals such as proteases or pH stress may also contribute, as does inhibition of the tyrosine phosphatase, TbPTP1. Further differentiation events occur in the tsetse to produce mature metacyclic forms in the salivary glands. These are pre-adapted to life in the mammalian host
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Fig1: A simplified depiction of the T. brucei life cycle. In the bloodstream of the mammalian host, slender forms proliferate. As density increases, the parasites produce stumpy induction factor (SIF) which induces differentiation of a proportion of slender forms to stumpy forms. Stumpy forms are pre-adapted to life in the tsetse vector: they are cell cycle-arrested and have elaborated mitochondrial activity. Upon uptake in a tsetse blood-meal, stumpy forms differentiate into the proliferative procyclic forms in response to cold shock and cis-aconitate or citrate (CCA) in the tsetse midgut. Other signals such as proteases or pH stress may also contribute, as does inhibition of the tyrosine phosphatase, TbPTP1. Further differentiation events occur in the tsetse to produce mature metacyclic forms in the salivary glands. These are pre-adapted to life in the mammalian host

Mentions: Trypanosomes differentiate between distinct life stages in order to prepare for, and adapt to, the different environments they encounter during their life cycle [2, 3]. During the bloodstream stage of the life cycle, trypanosomes exist as either proliferative ‘slender forms’ or non-proliferative, transmissible, ‘stumpy forms’ [2, 3] (Fig. 1), with transitional forms between these two types being described as ‘intermediate’ forms. The proportion of these types changes during the course of infection, this apparently being governed by the density of parasites in the blood. The bloodstream trypanosome population is adapted to promote parasite maintenance in the mammalian blood and transmission to tsetse flies. Thus, the proliferation of slender forms contributes to the establishment of parasite numbers in the blood and, through antigen variation, to immune evasion. In contrast, the irreversible division-arrest of stumpy forms acts to control the expansion of parasite numbers in the mammalian bloodstream and so prolongs host survival. This, combined with the preferential survival and the adaptations for differentiation of stumpy forms upon tsetse uptake, increases the probability of disease transmission [4].Fig. 1


New discoveries in the transmission biology of sleeping sickness parasites: applying the basics.

MacGregor P, Matthews KR - J. Mol. Med. (2010)

A simplified depiction of the T. brucei life cycle. In the bloodstream of the mammalian host, slender forms proliferate. As density increases, the parasites produce stumpy induction factor (SIF) which induces differentiation of a proportion of slender forms to stumpy forms. Stumpy forms are pre-adapted to life in the tsetse vector: they are cell cycle-arrested and have elaborated mitochondrial activity. Upon uptake in a tsetse blood-meal, stumpy forms differentiate into the proliferative procyclic forms in response to cold shock and cis-aconitate or citrate (CCA) in the tsetse midgut. Other signals such as proteases or pH stress may also contribute, as does inhibition of the tyrosine phosphatase, TbPTP1. Further differentiation events occur in the tsetse to produce mature metacyclic forms in the salivary glands. These are pre-adapted to life in the mammalian host
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2921060&req=5

Fig1: A simplified depiction of the T. brucei life cycle. In the bloodstream of the mammalian host, slender forms proliferate. As density increases, the parasites produce stumpy induction factor (SIF) which induces differentiation of a proportion of slender forms to stumpy forms. Stumpy forms are pre-adapted to life in the tsetse vector: they are cell cycle-arrested and have elaborated mitochondrial activity. Upon uptake in a tsetse blood-meal, stumpy forms differentiate into the proliferative procyclic forms in response to cold shock and cis-aconitate or citrate (CCA) in the tsetse midgut. Other signals such as proteases or pH stress may also contribute, as does inhibition of the tyrosine phosphatase, TbPTP1. Further differentiation events occur in the tsetse to produce mature metacyclic forms in the salivary glands. These are pre-adapted to life in the mammalian host
Mentions: Trypanosomes differentiate between distinct life stages in order to prepare for, and adapt to, the different environments they encounter during their life cycle [2, 3]. During the bloodstream stage of the life cycle, trypanosomes exist as either proliferative ‘slender forms’ or non-proliferative, transmissible, ‘stumpy forms’ [2, 3] (Fig. 1), with transitional forms between these two types being described as ‘intermediate’ forms. The proportion of these types changes during the course of infection, this apparently being governed by the density of parasites in the blood. The bloodstream trypanosome population is adapted to promote parasite maintenance in the mammalian blood and transmission to tsetse flies. Thus, the proliferation of slender forms contributes to the establishment of parasite numbers in the blood and, through antigen variation, to immune evasion. In contrast, the irreversible division-arrest of stumpy forms acts to control the expansion of parasite numbers in the mammalian bloodstream and so prolongs host survival. This, combined with the preferential survival and the adaptations for differentiation of stumpy forms upon tsetse uptake, increases the probability of disease transmission [4].Fig. 1

Bottom Line: One developmental form, the bloodstream stumpy stage, plays an important role in infection dynamics and transmission of the parasite.These molecular advances now provide improved experimental tools for the study of stumpy formation and function within the mammalian bloodstream.Here, we shall discuss the recent advances that have been made and the prospects for future research now available.

View Article: PubMed Central - PubMed

Affiliation: Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Kings Buildings, West Mains Road, Edinburgh, EH9 3JT, UK.

ABSTRACT
The sleeping sickness parasite, Trypanosoma brucei, must differentiate in response to the changing environments that it encounters during its complex life cycle. One developmental form, the bloodstream stumpy stage, plays an important role in infection dynamics and transmission of the parasite. Recent advances have shed light on the molecular mechanisms by which these stumpy forms differentiate as they are transmitted from the mammalian host to the insect vector of sleeping sickness, tsetse flies. These molecular advances now provide improved experimental tools for the study of stumpy formation and function within the mammalian bloodstream. They also offer new routes to therapy via high-throughput screens for agents that accelerate parasite development. Here, we shall discuss the recent advances that have been made and the prospects for future research now available.

Show MeSH
Related in: MedlinePlus