Biology of African trypanosomes in the tsetse fly

Vickerman, K.; Tetley, Laurence; Hendry, K. A. K.; Turner, C. Michael R.

doi:10.1016/0248-4900(88)90070-6

Cited by 175 publications

(142 citation statements)

References 21 publications

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“…Then, they migrate into the ectoperitrophic space that is between the peritrophic membrane and gut epithelium. In this space, digestive enzymes are inactive, and the procyclics are thought to divide actively (38)(39)(40). The fact that TbGPI10-disrupted procyclics had a lower ability to establish Effect of defective GPI anchor biosynthesis on the infection of procyclic T. brucei in tsetse fly midgut.…”

Section: Tbgpi10 Is Not Essential But Important For Growth Of Procyclmentioning

confidence: 99%

Critical roles of glycosylphosphatidylinositol for Trypanosoma brucei

Nagamune

Nozaki

Maeda

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

167

162

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Trypanosoma brucei, the protozoan parasite responsible for sleeping sickness, evades the immune response of mammalian hosts and digestion in the gut of the insect vector by means of its coat proteins tethered to the cell surface via glycosylphosphatidylinositol (GPI) anchors. To evaluate the importance of GPI for parasite survival, we cloned and disrupted a trypanosomal gene, TbGPI10, involved in biosynthesis of GPI. TbGPI10 encodes a protein of 558 amino acids having 25% and 23% sequence identity to human PIG-B and Saccharomyces cerevisiae Gpi10p, respectively. TbGPI10 restored biosynthesis of GPI in a mouse mutant cell line defective in mouse Pig-b gene. TbGPI10 also rescued the inviability of GPI10-disrupted S. cerevisiae, indicating that TbGPI10 is the orthologue of PIG-B͞GPI10 that is involved in the transfer of the third mannose to GPI. The bloodstream form of T. brucei could not lose TbGPI10; therefore, GPI synthesis is essential for growth of mammalian stage parasites. Procyclic form cells (insect stage parasites) lacking the surface coat proteins because of disruption of TbGPI10 are viable and grow slower than normal, provided that they are cultured in nonadherent flasks. In regular flasks, they adhered to the plastic surface and died. Infectivity to tsetse flies is partially impaired, particularly in the early stage. Therefore, parasitespecific inhibition of GPI biosynthesis should be an effective chemotherapy target against African trypanosomiasis.T rypanosoma brucei is a protozoan parasite invading humans and other mammals by transmission via tsetse flies. It causes sleeping sickness in humans and nagana disease in domestic animals living in the ''tsetse belt'' in central Africa. These are serious medical and agricultural problems for which safe and effective therapeutic and protective measures are highly desirable (1, 2).T. brucei has two distinct proliferative stages, a bloodstream stage living free in mammalian blood and an insect stage (or procyclic form) living in the midguts of tsetse flies. The cell surface of both stages of this unicellular parasite is covered by a large amount of glycosylphosphatidylinositol (GPI)-anchored proteins (3, 4): 10 7 variant surface glycoproteins per cell for the bloodstream form of the parasite and 3 ϫ 10 6 to 6 ϫ 10 6 procyclins (or procyclic acidic repetitive proteins) per cell of the procyclic form of the parasite (4-6), corresponding to 10% and 1-3%, respectively, of total proteins in these parasite stages (7,8). T. brucei evades the host's immune response by expressing structurally different forms of variant surface glycoproteins (4). Procyclins are thought to protect procyclic cells from digestion by the digestive enzymes in the fly (4, 6). In addition, T. brucei expresses a number of other GPI-anchored proteins, such as transferrin receptors in the bloodstream form (3, 4). Thus, the importance of GPI anchors for the survival and infection of T. brucei has been suggested, leading to the notion that the GPI biosynthesis pathway may be a good target for chemo...

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Section: Tbgpi10 Is Not Essential But Important For Growth Of Procyclmentioning

confidence: 99%

Critical roles of glycosylphosphatidylinositol for Trypanosoma brucei

Nagamune

Nozaki

Maeda

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

167

162

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“…Because the kinetoplast is maintained at a specific position yet the single mitochondrion extends along the length of the cell (Vickerman, 1965;Simpson, 1972;Vickerman et al, 1988), there is a strong suggestion that some structure links the kDNA within the mitochondrial lumen to a particular position on the inner mitochondrial membrane. Moreover, this structure should presumably be positioned directly opposite the basal bodies.…”

Section: Unilateral Kinetoplast Filaments Of Tacmentioning

confidence: 99%

A High-OrderTrans-Membrane Structural Linkage Is Responsible for Mitochondrial Genome Positioning and Segregation by Flagellar Basal Bodies in Trypanosomes

Ogbadoyi

Robinson

Gull

2003

MBoC

237

279

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In trypanosomes, the large mitochondrial genome within the kinetoplast is physically connected to the flagellar basal bodies and is segregated by them during cell growth. The structural linkage enabling these phenomena is unknown. We have developed novel extraction/fixation protocols to characterize the links involved in kinetoplast-flagellum attachment and segregation. We show that three specific components comprise a structure that we have termed the tripartite attachment complex (TAC). The TAC involves a set of filaments linking the basal bodies to a zone of differentiated outer and inner mitochondrial membranes and a further set of intramitochondrial filaments linking the inner face of the differentiated membrane zone to the kinetoplast. The TAC and flagellum-kinetoplast DNA connections are sustained throughout the cell cycle and are replicated and remodeled during the periodic kinetoplast DNA S phase. This understanding of the high-order trans-membrane linkage provides an explanation for the spatial position of the trypanosome mitochondrial genome and its mechanism of segregation. Moreover, the architecture of the TAC suggests that it may also function in providing a structural and vectorial role during replication of this catenated mass of mitochondrial DNA. We suggest that this complex may represent an extreme form of a more generally occurring mitochondrion/cytoskeleton interaction. INTRODUCTIONThe African trypanosome Trypanosoma brucei belongs to a large order of pathogenic and free-living flagellated protozoa designated the kinetoplastida. The majority of these organisms possess a single mitochondrion containing a structural mass of proteins and catenated circular DNA molecules, the kinetoplast. The kinetoplast is essential for survival and cyclical transmission of the parasite between mammalian host and tsetse fly. Early light microscope descriptions of trypanosomes recognized the precise location of the kinetoplast in proximity to the base of the flagellum (Robertson, 1912(Robertson, , 1913. The positions of the flagellum and kinetoplast have become the central features in classifying the different life cycle stages of kinetoplastids (Hoare and Wallace, 1966;Vickerman, 1976). Electron microscopy revealed the kinetoplast to be a highly complex disk-shaped structure located within a distended portion of the mitochondrial matrix adjacent to the flagellum basal bodies (Vickerman, 1973). The T. brucei kinetoplast consists of multiple copies of topologically interlocked circular DNA molecules termed maxicircles and minicircles, along with specific kinetoplast proteins. The maxicircle composition of the T. brucei network is 25-50 copies and represents 10% of the network mass (each maxicircle is 20 kb and all have identical DNA sequence). Maxicircles encode the mitochondrial proteins and some guide RNAs (gRNAs), whereas the minicircles are present in several thousand copies (1 kb in length), are heterogeneous in sequence, and encode gRNAs. The gRNAs are essential for the RNA editing process whereby the maxic...

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“…When stumpy forms of T. b. brucei are taken up by the tsetse fly, they differentiate into procyclic forms in the endoperitrophic space [13]. Early procyclic forms can be recognised by their expression of a GPI-anchored protein, GPEET procyclin, which is expressed exclusively by this stage of the life cycle [14,15].…”

Section: Coordinated Group Movement -The Phenomenon Of Social Motilitymentioning

confidence: 99%

The languages of parasite communication

Roditi

2016

Molecular and Biochemical Parasitology

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Although it is regarded as self-evident that parasites interact with their hosts, with the primary aim of enhancing their own survival and transmission, the extent to which unicellular parasites communicate with each has been severely underestimated.Recent publications show that information is commonly exchanged between parasites of the same species and that this can govern their decisions to divide, to differentiate or to migrate as a group. Communication can take the form of soluble secreted factors, extracellular vesicles or contact between cells. Extracellular parasites can do this directly, while intracellular parasites use the infected host cell -or components derived from it -as an intermediary. By emitting signals that can be dispersed within the host, parasites can also have long-distance effects on the course of an infection and its pathology. This article presents an overview of recent developments in this field and draws attention to some older work that merits re-examination. 3 Most readers of this article will not need to be told that diseases such as sleeping sickness, malaria, Leishmaniasis, Trichomoniasis and Chagas Disease are caused by unicellular parasites. This knowledge might come with the tacit assumption that singlecelled organisms are completely self-sufficient and have no need to interact, much less cooperate, with members of their own species. In recent years, however, it has become apparent that a number of decisions are group decisions that rely on parasites communicating with each other. Just as animals can exchange information in different ways, be it vocally, visually, chemically or by body language, parasites have also developed a range of mechanisms for communicating with each other. This sometimes occurs directly, from parasite to parasite, or by using the infected host cell -or components derived from it -as an intermediary. By emitting signals that can be dispersed within the host, parasites can also have wide-ranging effects on the course of an infection and its pathology. This article presents an overview of recent developments in this field and draws attention to some older work that merits re-examination. Owing to space constraints, it will not cover molecules used by intracellular parasites to reprogram the cells that they infect. Quorum sensing and differentiationDifferent subspecies of Trypanosoma brucei, the pathogens responsible for human sleeping sickness and Nagana in domestic animals, are extracellular throughout their life cycle. In the mammalian host the parasites use a quorum sensing mechanism to maintain a balance between slender bloodstream forms, which are capable of dividing every 6-8 hours, and stumpy bloodstream forms, which cannot divide and have a lifespan of a few days. When trypanosomes ingested by a tsetse fly, the slender form is killed while the stumpy form survives and differentiates to the next life stage, the procyclic form, in the insect midgut [1,2]. If slender forms were to proliferate unchecked, this would result in rapid death of th...

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Biology of African trypanosomes in the tsetse fly

Cited by 175 publications

References 21 publications

Critical roles of glycosylphosphatidylinositol for Trypanosoma brucei

Critical roles of glycosylphosphatidylinositol for Trypanosoma brucei

A High-OrderTrans-Membrane Structural Linkage Is Responsible for Mitochondrial Genome Positioning and Segregation by Flagellar Basal Bodies in Trypanosomes

The languages of parasite communication

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