In vitro trypanocidal effect of sera from Erythrocebus patas (Red Patas monkey) and Chlorocebus tantalus (Tantalus monkey) on Trypanosoma brucei brucei Plimmer & Bradford, 1899 and Trypanosoma congolense Broden, 1894

ABSTRACTAnti-Trypanosoma brucei brucei and anti-Trypanosoma congolense activities of sera from two species of uninfected zoo-primates, Erythrocebus patas (red patas monkey) and Chlorocebus tantalus (tantalus monkey) were investigated. The sera were screened using thick films and haematocrit centrifugation technique (HCT), to ensure that the donor primates were not infected with trypanosomes. Trypanosoma brucei brucei (Federe strain) and Trypanosoma congolense were suspended in supplemented RPMI (Rossvelt Park Memorial Institute) 1640 medium and the motility of the parasite was used as index of viability after the addition of each test serum. The selected primate sera exhibited some degree of anti-Trypanosoma brucei brucei activities in vitro. Red patas monkey serum had an inhibition index of 0.27, while that of Tantalus monkey was 0.34, against Trypanosoma brucei brucei, with mean survival times of 22.00±1.73 hours for red patas monkey serum and 19.67±0.58 hours for tantalus monkey serum, which are significantly lower (P<0.05) than that of the control (30.00±0.00 hours). The selected primate sera had pronounced inhibitory activities against Trypanosoma congolense. Sera from the two species of primate had very high anti-Trypanosoma congolense activity showing an inhibition index of 0.91 for Red patas monkey serum and 0.90 for Tantalus monkey serum, with marked and significant reduction (P<0.05) in survival time of 7.00±1.73 hours in Red patas monkey serum and 7.67±0.58 hours in Tantalus monkey serum, compared with the control (74.00±1.00 hours). The in vitro anti-trypanosomal activity of the serum samples was shown to be cidal in nature. The activity was not associated with xanthine oxidase. This study revealed that sera from red patas monkey and tantalus monkey had a moderate anti-Trypanosoma brucei brucei activity and a very high anti-Trypanosoma congolense activity in vitro suggesting the presence of some non-specific materials.Authors’ SummaryThe mechanisms that allow trypanosomiasis-resistant animals to control blood trypanosomes are being investigated, to identify non-specific factors that kill trypanosomes or limit their proliferation, contributing to host resistance. For instance, xanthine oxidase has been isolated and identified as the protein that kills trypanosomes in Cape buffalo. Humans and several other primates are also known to be resistant to infection by several animal-specific trypanosome species. In this study, sera from some zoo primates, red patas monkey and tantalus monkey, tested on Trypanosoma brucei brucei and Trypanosoma congolense in vitro, showed a slight anti-Trypanosoma brucei brucei activity and a very high anti-Trypanosoma congolense activity. These activities were shown to be cidal in nature and not associated with the protein xanthine oxidase. The authors suggest that non-specific factors other than the enzyme xanthine oxidase might have accounted for the sera anti-trypanosomal activities.

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Comparison of the cytolytic effects in vitro on Trypanosoma brucei brucei of plasma, high density lipoproteins, and apolipoprotein A-I from hosts both susceptible (cattle and sheep) and resistant (human and baboon) to infection.

The Journal of Lipid Research ◽

10.1016/s0022-2275(20)41617-7 ◽

1992 ◽

Vol 33 (4) ◽

pp. 513-523

Author(s):

MP Gillett ◽

JS Owen

Keyword(s):

Trypanosoma Brucei ◽

High Density ◽

High Density Lipoproteins ◽

Trypanosoma Brucei Brucei ◽

Apolipoprotein A ◽

Plasma High Density ◽

Cattle And Sheep

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Cross-Resistance to Nitro Drugs and Implications for Treatment of Human African Trypanosomiasis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00332-10 ◽

2010 ◽

Vol 54 (7) ◽

pp. 2893-2900 ◽

Cited By ~ 69

Author(s):

Antoaneta Y. Sokolova ◽

Susan Wyllie ◽

Stephen Patterson ◽

Sandra L. Oza ◽

Kevin D. Read ◽

...

Keyword(s):

Trypanosoma Brucei ◽

Human African Trypanosomiasis ◽

Parent Drug ◽

Cross Resistance ◽

Pharmacokinetic Studies ◽

African Trypanosomiasis ◽

Trypanosoma Brucei Brucei ◽

Resistant Lines

ABSTRACT The success of nifurtimox-eflornithine combination therapy (NECT) for the treatment of human African trypanosomiasis (HAT) has renewed interest in the potential of nitro drugs as chemotherapeutics. In order to study the implications of the more widespread use of nitro drugs against these parasites, we examined the in vivo and in vitro resistance potentials of nifurtimox and fexinidazole and its metabolites. Following selection in vitro by exposure to increasing concentrations of nifurtimox, Trypanosoma brucei brucei nifurtimox-resistant clones designated NfxR1 and NfxR2 were generated. Both cell lines were found to be 8-fold less sensitive to nifurtimox than parental cells and demonstrated cross-resistance to a number of other nitro drugs, most notably the clinical trial candidate fexinidazole (∼27-fold more resistant than parental cells). Studies of mice confirmed that the generation of nifurtimox resistance in these parasites did not compromise virulence, and NfxR1 remained resistant to both nifurtimox and fexinidazole in vivo. In the case of fexinidazole, drug metabolism and pharmacokinetic studies indicate that the parent drug is rapidly metabolized to the sulfoxide and sulfone form of this compound. These metabolites retained trypanocidal activity but were less effective in nifurtimox-resistant lines. Significantly, trypanosomes selected for resistance to fexinidazole were 10-fold more resistant to nifurtimox than parental cells. This reciprocal cross-resistance has important implications for the therapeutic use of nifurtimox in a clinical setting and highlights a potential danger in the use of fexinidazole as a monotherapy.

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Diminazene aceturate residues in the tissues of healthy, Trypanosoma congolense and Trypanosoma brucei brucei infected dogs

British Veterinary Journal ◽

10.1016/0007-1935(91)90106-w ◽

1991 ◽

Vol 147 (2) ◽

pp. 155-162 ◽

Cited By ~ 16

Author(s):

P.A. Onyeyili ◽

S.M. Anika

Keyword(s):

Trypanosoma Brucei ◽

Trypanosoma Congolense ◽

Trypanosoma Brucei Brucei ◽

Diminazene Aceturate

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An antibiotic, ascofuranone, specifically inhibits respiration and in vitro growth of long slender bloodstream forms of Trypanosoma brucei brucei

Molecular and Biochemical Parasitology ◽

10.1016/0166-6851(96)02665-5 ◽

1996 ◽

Vol 81 (2) ◽

pp. 127-136 ◽

Cited By ~ 41

Author(s):

Nobuko Minagawa ◽

Yoshisada Yabu ◽

Kiyoshi Kita ◽

Kazuo Nagai ◽

Nobuo Ohta ◽

...

Keyword(s):

Trypanosoma Brucei ◽

In Vitro Growth ◽

Trypanosoma Brucei Brucei

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In Vitro, In Vivo and Phytochemical Screening, of Extracts of Piper guineense for trypanocidal Activities Against Trypanosoma brucei brucei.

International Journal of Biology ◽

10.5539/ijb.v5n3p85 ◽

2013 ◽

Vol 5 (3) ◽

Cited By ~ 2

Author(s):

J. A. Abedo ◽

A. O. Jonah ◽

M. R. Mazadu ◽

R. S. Abdullahi ◽

H. Y. Idris ◽

...

Keyword(s):

Trypanosoma Brucei ◽

Phytochemical Screening ◽

Trypanosoma Brucei Brucei ◽

Piper Guineense

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In Vitro Generation of Human High-Density-Lipoprotein-Resistant Trypanosoma brucei brucei

Eukaryotic Cell ◽

10.1128/ec.00116-06 ◽

2006 ◽

Vol 5 (8) ◽

pp. 1276-1286 ◽

Cited By ~ 15

Author(s):

Sara D. Faulkner ◽

Monika W. Oli ◽

Rudo Kieft ◽

Laura Cotlin ◽

Justin Widener ◽

...

Keyword(s):

High Density Lipoprotein ◽

Trypanosoma Brucei ◽

Density Lipoprotein ◽

High Density ◽

Surface Glycoprotein ◽

Trypanosoma Brucei Brucei ◽

African Trypanosomes ◽

Expression Site ◽

Human High Density Lipoprotein

ABSTRACT The host range of African trypanosomes is influenced by innate protective molecules in the blood of primates. A subfraction of human high-density lipoprotein (HDL) containing apolipoprotein A-I, apolipoprotein L-I, and haptoglobin-related protein is toxic to Trypanosoma brucei brucei but not the human sleeping sickness parasite Trypanosoma brucei rhodesiense. It is thought that T. b. rhodesiense evolved from a T. b. brucei-like ancestor and expresses a defense protein that ablates the antitrypanosomal activity of human HDL. To directly investigate this possibility, we developed an in vitro selection to generate human HDL-resistant T. b. brucei. Here we show that conversion of T. b. brucei from human HDL sensitive to resistant correlates with changes in the expression of the variant surface glycoprotein (VSG) and abolished uptake of the cytotoxic human HDLs. Complete transcriptome analysis of the HDL-susceptible and -resistant trypanosomes confirmed that VSG switching had occurred but failed to reveal the expression of other genes specifically associated with human HDL resistance, including the serum resistance-associated gene (SRA) of T. b. rhodesiense. In addition, we found that while the original active expression site was still utilized, expression of three expression site-associated genes (ESAG) was altered in the HDL-resistant trypanosomes. These findings demonstrate that resistance to human HDLs can be acquired by T. b. brucei.

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Isothiochromenothiazoles—A Class of Fused Thiazolidinone Derivatives with Established Anticancer Activity That Inhibits Growth of Trypanosoma brucei brucei

Scientia Pharmaceutica ◽

10.3390/scipharm86040047 ◽

2018 ◽

Vol 86 (4) ◽

pp. 47 ◽

Cited By ~ 4

Author(s):

Anna Kryshchyshyn ◽

Danylo Kaminskyy ◽

Igor Nektegayev ◽

Philippe Grellier ◽

Roman Lesyk

Keyword(s):

Acute Toxicity ◽

Anticancer Activity ◽

Trypanosoma Brucei ◽

In Vitro Assay ◽

Parasite Growth ◽

Trypanosoma Brucei Brucei ◽

Vitro Assay ◽

Antiparasitic Agents ◽

Micromolar Range

Recently, thiazolidinone derivatives have been widely studied as antiparasitic agents. Previous investigations showed that fused 4-thiazolidinone derivatives (especially thiopyranothiazoles) retain pharmacological activity of their synthetic precursors—simple 5-ene-4-thiazolidinones. A series of isothiochromeno[4a,4-d][1,3] thiazoles was investigated in an in vitro assay towards bloodstream forms of Trypanosoma brucei brucei. All compounds inhibited parasite growth at concentrations in the micromolar range. The established low acute toxicity of this class of compounds along with a good trypanocidal profile indicates that isothiochromenothiazole derivatives may be promising for designing new antitrypanosomal drugs.

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