Adaptation and therapeutic exploitation of the plasma membrane of African trypanosomes

Research output: Contribution to journalReview article

Abstract

African trypanosomes are highly divergent from their metazoan hosts, and as part of adaptation to a parasitic life style have developed a unique endomembrane system. The key virulence mechanism of many pathogens is successful immune evasion, to enable survival within a host, a feature that requires both genetic events and membrane transport mechanisms in African trypanosomes. Intracellular trafficking not only plays a role in immune evasion, but also in homeostasis of intracellular and extracellular compartments and interactions with the environment. Significantly, historical and recent work has unraveled some of the connections between these processes and highlighted how immune evasion mechanisms that are associated with adaptations to membrane trafficking may have, paradoxically, provided specific sensitivity to drugs. Here, we explore these advances in understanding the membrane composition of the trypanosome plasma membrane and organelles and provide a perspective for how transport could be exploited for therapeutic purposes.
LanguageEnglish
Article number368
Number of pages16
JournalGenes
Volume9
Issue number7
DOIs
Publication statusPublished - 20 Jul 2018

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Immune Evasion
Trypanosomiasis
Cell Membrane
Membranes
Organelles
Virulence
Life Style
Homeostasis
Therapeutics
Pharmaceutical Preparations

Keywords

  • Trypanosoma brucei
  • surface proteome
  • endomembrane system
  • endocytosis
  • drug development
  • nanobodies

Cite this

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title = "Adaptation and therapeutic exploitation of the plasma membrane of African trypanosomes",
abstract = "African trypanosomes are highly divergent from their metazoan hosts, and as part of adaptation to a parasitic life style have developed a unique endomembrane system. The key virulence mechanism of many pathogens is successful immune evasion, to enable survival within a host, a feature that requires both genetic events and membrane transport mechanisms in African trypanosomes. Intracellular trafficking not only plays a role in immune evasion, but also in homeostasis of intracellular and extracellular compartments and interactions with the environment. Significantly, historical and recent work has unraveled some of the connections between these processes and highlighted how immune evasion mechanisms that are associated with adaptations to membrane trafficking may have, paradoxically, provided specific sensitivity to drugs. Here, we explore these advances in understanding the membrane composition of the trypanosome plasma membrane and organelles and provide a perspective for how transport could be exploited for therapeutic purposes.",
keywords = "Trypanosoma brucei, surface proteome, endomembrane system, endocytosis, drug development, nanobodies",
author = "Quintana, {Juan F.} and {Canavate Del Pino}, Ricardo and Kayo Yamada and Ning Zhang and Mark Field",
note = "This research was funded by the Medical Research Council grant number MR/N010558/1, MR/P009018/1] and the Wellcome Trust [204697/Z/16/Z] (all to M.C.F.). M.C.F. is a Wellcome Investigator.",
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T1 - Adaptation and therapeutic exploitation of the plasma membrane of African trypanosomes

AU - Quintana , Juan F.

AU - Canavate Del Pino, Ricardo

AU - Yamada, Kayo

AU - Zhang, Ning

AU - Field, Mark

N1 - This research was funded by the Medical Research Council grant number MR/N010558/1, MR/P009018/1] and the Wellcome Trust [204697/Z/16/Z] (all to M.C.F.). M.C.F. is a Wellcome Investigator.

PY - 2018/7/20

Y1 - 2018/7/20

N2 - African trypanosomes are highly divergent from their metazoan hosts, and as part of adaptation to a parasitic life style have developed a unique endomembrane system. The key virulence mechanism of many pathogens is successful immune evasion, to enable survival within a host, a feature that requires both genetic events and membrane transport mechanisms in African trypanosomes. Intracellular trafficking not only plays a role in immune evasion, but also in homeostasis of intracellular and extracellular compartments and interactions with the environment. Significantly, historical and recent work has unraveled some of the connections between these processes and highlighted how immune evasion mechanisms that are associated with adaptations to membrane trafficking may have, paradoxically, provided specific sensitivity to drugs. Here, we explore these advances in understanding the membrane composition of the trypanosome plasma membrane and organelles and provide a perspective for how transport could be exploited for therapeutic purposes.

AB - African trypanosomes are highly divergent from their metazoan hosts, and as part of adaptation to a parasitic life style have developed a unique endomembrane system. The key virulence mechanism of many pathogens is successful immune evasion, to enable survival within a host, a feature that requires both genetic events and membrane transport mechanisms in African trypanosomes. Intracellular trafficking not only plays a role in immune evasion, but also in homeostasis of intracellular and extracellular compartments and interactions with the environment. Significantly, historical and recent work has unraveled some of the connections between these processes and highlighted how immune evasion mechanisms that are associated with adaptations to membrane trafficking may have, paradoxically, provided specific sensitivity to drugs. Here, we explore these advances in understanding the membrane composition of the trypanosome plasma membrane and organelles and provide a perspective for how transport could be exploited for therapeutic purposes.

KW - Trypanosoma brucei

KW - surface proteome

KW - endomembrane system

KW - endocytosis

KW - drug development

KW - nanobodies

U2 - 10.3390/genes9070368

DO - 10.3390/genes9070368

M3 - Review article

VL - 9

JO - Genes

T2 - Genes

JF - Genes

SN - 2073-4425

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ER -