Regulation of surface coat exchange by differentiating African trypanosomes

Gruszynski, Amy E.; Deursen, Frederick J. van; Albareda, María Cecilia; Best, Alexander; Chaudhary, Kshitiz; Cliffe, Laura J.; Rı́o, Laura Del; Dunn, Joe Dan; Ellis, Louise; Evans, Krystal J.; Figueiredo, Juliana M.; Malmquist, Nicholas A.; Omosun, Yusuf; Palenchar, Jennifer B.; Prickett, Sara; Punkosdy, George A.; Dooren, Giel G. van; Wang, Qian; Menon, Anant K.; Matthews, Keith R.; Bangs, James D.

doi:10.1016/j.molbiopara.2006.02.013

Cited by 45 publications

(58 citation statements)

References 65 publications

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“…Differentiation from BSF to PCF trypanosomes is characterized by removal of the VSG surface coat and the acquisition of procyclin (40). Rapid shedding of VSG occurs mainly by endoproteolysis, mediated by zinc metalloprotease (MSP-B) activity and supported by glycosylphosphatidylinositol-specific phospholipase C-mediated glycosylphosphatidylinositol hydrolysis (16). A relatively low rate of loss of clathrin expression during the early phase of the differentiation process may facilitate efficient continued endocytosis and recycling of VSG and delivery to these hydrolases to complete surface remodeling.…”

Section: Discussionmentioning

confidence: 99%

Activation of Endocytosis as an Adaptation to the Mammalian Host by Trypanosomes

et al. 2007

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Immune evasion in African trypanosomes is principally mediated by antigenic variation, but rapid internalization of surface-bound immune factors may contribute to survival. Endocytosis is upregulated approximately 10-fold in bloodstream compared to procyclic forms, and surface coat remodeling accompanies transition between these life stages. Here we examined expression of endocytosis markers in tsetse fly stages in vivo and monitored modulation during transition from bloodstream to procyclic forms in vitro. Among bloodstream stages nonproliferative stumpy forms have endocytic activity similar to that seen with rapidly dividing slender forms, while differentiation of stumpy forms to procyclic forms is accompanied by rapid down-regulation of Rab11 and clathrin, suggesting that modulation of endocytic and recycling systems accompanies this differentiation event. Significantly, rapid down-regulation of endocytic markers occurs upon entering the insect midgut and expression of Rab11 and clathrin remains low throughout subsequent development, which suggests that high endocytic activity is not required for remodeling the parasite surface or for survival within the fly. However, salivary gland metacyclic forms dramatically increase expression of clathrin and Rab11, indicating that emergence of mammalian infective forms is coupled to reacquisition of a high-activity endocytic-recycling system. These data suggest that high-level endocytosis in Trypanosoma brucei is an adaptation required for viability in the mammalian host.

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Section: Discussionmentioning

confidence: 99%

Activation of Endocytosis as an Adaptation to the Mammalian Host by Trypanosomes

et al. 2007

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“…38). Stumpy parasites release their VSG coat via a bimodal process that involves GPI hydrolysis by a parasite GPI phospholipase C and endoproteolytic cleavage (39,40). Next, these parasites synthesize a new surface coat composed of GPI-anchored Procyclins (41), which are necessary for efficient colonization of the tsetse midgut (42).…”

Section: Mammalian Parasite Vsg Coat Proteins Mediate the Cardia Genementioning

confidence: 99%

Mammalian African trypanosome VSG coat enhances tsetse’s vector competence

Aksoy

Vigneron

Bing

et al. 2016

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

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Tsetse flies are biological vectors of African trypanosomes, the protozoan parasites responsible for causing human and animal trypanosomiases across sub-Saharan Africa. Currently, no vaccines are available for disease prevention due to antigenic variation of the Variant Surface Glycoproteins (VSG) that coat parasites while they reside within mammalian hosts. As a result, interference with parasite development in the tsetse vector is being explored to reduce disease transmission. A major bottleneck to infection occurs as parasites attempt to colonize tsetse's midgut. One critical factor influencing this bottleneck is the fly's peritrophic matrix (PM), a semipermeable, chitinous barrier that lines the midgut. The mechanisms that enable trypanosomes to cross this barrier are currently unknown. Here, we determined that as parasites enter the tsetse's gut, VSG molecules released from trypanosomes are internalized by cells of the cardiathe tissue responsible for producing the PM. VSG internalization results in decreased expression of a tsetse microRNA (mir-275) and interferes with the Wnt-signaling pathway and the Iroquois/IRX transcription factor family. This interference reduces the function of the PM barrier and promotes parasite colonization of the gut early in the infection process. Manipulation of the insect midgut homeostasis by the mammalian parasite coat proteins is a novel function and indicates that VSG serves a dual role in trypanosome biology-that of facilitating transmission through its mammalian host and insect vector. We detail critical steps in the course of trypanosome infection establishment that can serve as novel targets to reduce the tsetse's vector competence and disease transmission.tsetse | trypanosome | VSG | peritrophic matrix | vector competence

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“…A further detailed analysis provides evidence for a coordinated and inverse regulation of the activities of MSP-B and PLC during synchronous differentiation. MSP-B upregulation is inversely reflected by PLC downregulation, with the latter playing only a quantitatively minor role during differentiation (43).…”

Section: Tbmsp-bmentioning

confidence: 99%

Major Surface Protease of Trypanosomatids: One Size Fits All?

Yao

2010

Infect Immun

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Trypanosomatids are a very diverse group of protozoa including many species of medical, veterinary, and/or economical importance. Leishmania spp. cause disease on the continents of Asia, Africa, Europe, and North and South America; Trypanosoma cruzi is the etiology of Chagas' disease in South and Central America; and Trypanosoma brucei infections result in African sleeping sickness. Four genera of heteroxenous trypanosomatids transmitted by insect vectors infect a wide range of hosts including humans, animals, and plants. Six genera of monoxenous trypanosomatids parasitize numerous species of insects. Due to this diversity, the life cycle of Leishmania spp. is presented as a model to which other heteroxenous and monoxenous groups will be briefly contrasted.During their life cycle, Leishmania spp. shuttle between a flagellated promastigote stage in the sand fly vector and a nonmotile amastigote stage in a mammalian host. During blood meals on infected hosts, the sand fly vectors ingest amastigote-laden macrophages (Mø). These amastigotes transform to procyclic promastigotes in the sand fly gut, multiply by binary fission, and eventually develop into metacyclic promastigotes, the infective stage for mammalian hosts including humans. The sand fly vectors, upon taking another blood meal, inoculate the metacyclic promastigotes into the dermis, where they are phagocytized by Mø of the mammalian hosts. Amastigotes, transformed from metacyclic promastigotes, multiply in parasitophorous vacuoles (PV) of the host's Mø. Multiplication of amastigotes eventually leads to rupture of the infected Mø and release of amastigotes, which infect additional Mø, perpetuating the cycle of replication (38).Other , Crithidia, Leptomonas, Herpetomonas, Rhynchoidomonas, and Phytomonas (87). Leishmania spp. harbor a zinc metalloprotease, discovered in the mid-1980s, on their surfaces (14,15,36,37,88). This enzyme, accounting for about 1% of the total protein in promastigotes of Leishmania major and Leishmania mexicana (2, 10) and being potentially important during different stages of the life cycle, soon became the object of much investigation (8,70,71,107). Although referred to here as major surface protease (MSP), this zinc metalloprotease has also been termed GP63, surface acid protease, promastigote surface protease, EC 3.4.24.36, and leishmanolysin.MSPs of Leishmania spp. belong to the M8 family of endopeptidases, sharing several characteristics with mammalian matrix metalloproteases. Similarities include degradation of the extracellular matrix, cell surface localization, protease activity requiring Zn 2ϩ , and inhibition of protease activity by * Mailing address:

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Regulation of surface coat exchange by differentiating African trypanosomes

Cited by 45 publications

References 65 publications

Activation of Endocytosis as an Adaptation to the Mammalian Host by Trypanosomes

Activation of Endocytosis as an Adaptation to the Mammalian Host by Trypanosomes

Mammalian African trypanosome VSG coat enhances tsetse’s vector competence

Major Surface Protease of Trypanosomatids: One Size Fits All?

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