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The Trypanosomal Transferrin Receptor of Trypanosoma Brucei-A Review.

ABSTRACT: Iron is an essential element for life. Its uptake and utility requires a careful balancing with its toxic capacity, with mammals evolving a safe and bio-viable means of its transport and storage. This transport and storage is also utilized as part of the iron-sequestration arsenal employed by the mammalian hosts' 'nutritional immunity' against parasites. Interestingly, a key element of iron transport, i.e., serum transferrin (Tf), is an essential growth factor for parasitic haemo-protozoans of the genus Trypanosoma. These are major mammalian parasites causing the diseases human African trypanosomosis (HAT) and animal trypanosomosis (AT). Using components of their well-characterized immune evasion system, bloodstream Trypanosoma brucei parasites adapt and scavenge for the mammalian host serum transferrin within their broad host range. The expression site associated genes (ESAG6 and 7) are utilized to construct a heterodimeric serum Tf binding complex which, within its niche in the flagellar pocket, and coupled to the trypanosomes' fast endocytic rate, allows receptor-mediated acquisition of essential iron from their environment. This review summarizes current knowledge of the trypanosomal transferrin receptor (TfR), with emphasis on the structure and function of the receptor, both in physiological conditions as well as in conditions where the iron supply to parasites is being limited. Potential applications using current knowledge of the parasite receptor are also briefly discussed, primarily focused on potential therapeutic interventions.

SUBMITTER: Kariuki CK

PROVIDER: S-EPMC6958415 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Project description:We assessed the virulence and anti-trypanosomal drug sensitivity patterns of Trypanosoma brucei rhodesiense (Tbr) isolates in the Kenya Agricultural and Livestock Research Organization-Biotechnology Research Institute (KALRO-BioRI) cryobank. Specifically, the study focused on Tbr clones originally isolated from the western Kenya/eastern Uganda focus of human African Trypanosomiasis (HAT). Twelve (12) Tbr clones were assessed for virulence using groups(n = 10) of Swiss White Mice monitored for 60 days post infection (dpi). Based on survival time, four classes of virulence were identified: (a) very-acute: 0-15, (b) acute: 16-30, (c) sub-acute: 31-45 and (d) chronic: 46-60 dpi. Other virulence biomarkers identified included: pre-patent period (pp), parasitaemia progression, packed cell volume (PCV) and body weight changes. The test Tbr clones together with KALRO-BioRi reference drug-resistant and drug sensitive isolates were then tested for sensitivity to melarsoprol (mel B), pentamidine, diminazene aceturate and suramin, using mice groups (n = 5) treated with single doses of each drug at 24 hours post infection. Our results showed that the clones were distributed among four classes of virulence as follows: 3/12 (very-acute), 3/12 (acute), 2/12 (sub-acute) and 4/12 (chronic) isolates. Differences in survivorship, parasitaemia progression and PCV were significant (P<0.001) and correlated. The isolate considered to be drug resistant at KALRO-BioRI, KETRI 2538, was confirmed to be resistant to melarsoprol, pentamidine and diminazene aceturate but it was not resistant to suramin. A cure rate of at least 80% was achieved for all test isolates with melarsoprol (1mg/Kg and 20 mg/kg), pentamidine (5 and 20 mg/kg), diminazene aceturate (5 mg/kg) and suramin (5 mg/kg) indicating that the isolates were not resistant to any of the drugs despite the differences in virulence. This study provides evidence of variations in virulence of Tbr clones from a single HAT focus and confirms that this variations is not a significant determinant of isolate sensitivity to anti-trypanosomal drugs.

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The Trypanosomal Transferrin Receptor of Trypanosoma Brucei-A Review.

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