Population genetic structure and cladistic analysis of Trypanosoma brucei isolates

Agbo, Eddy Chukwura; Clausen, Peter‐Henning; Büscher, Philippe; Majiwa, Phelix A.O.; Claassen, Eric; Pas, M.F.W. te

doi:10.1016/s1567-1348(03)00071-6

Cited by 7 publications

(9 citation statements)

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“…This PCR test is based on the assumption that human serum resistant trypanosomes have the sra gene and non-human infective trypanosomes do not which appears to hold true for the majority of isolates tested from east and southern Africa Welburn et al 2001;Agbo et al 2003), but not for west and central Africa (Berberof et al 2001;Radwanska et al 2002).…”

Section: Discussionmentioning

confidence: 99%

“…However, while it is clear that the sra gene is responsible for human infectivity in a large number of T. b. rhodesiense isolates Welburn et al 2001), there are exceptions to this in trypanosome lines from East Africa (Rifkin et al 1994;Agbo et al 2003) and, critically, this gene is not present in West African T. b. gambiense isolates (De Greef and Hamers 1994;Radwanska et al 2002). Thus there must be alternative mechanisms determining human infectivity/human serum resistance other than those based on the sra gene.…”

Section: Introductionmentioning

confidence: 99%

“…A PCR-based method for the detection of the sra gene has been developed and the presence of the gene has been shown to correlate strongly with the human serum-resistant (HSR) phenotype in the Busoga focus, and so this method has been heralded as a means of defining human infective trypanosomes (Welburn et al 2001). However, while it is clear that the sra gene is responsible for human infectivity in a large number of T. b. rhodesiense isolates (Welburn et al 2001 ;Gibson et al 2002), there are exceptions to this in trypanosome lines from East Africa (Rifkin et al 1994 ;Agbo et al 2003) and, critically, this gene is not present in West African T. b. gambiense isolates (De Greef & Hamers, 1994 ;Radwanska et al 2002). Thus, there must be alternative mechanisms determining human infectivity/human serum resistance other than those based on the sra gene.…”

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confidence: 99%

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Human infectivity trait in Trypanosoma brucei: stability, heritability and relationship to sra expression

et al. 2004

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Email: m.turner@bio.gla.ac.ukT SUMMARY Some Trypanosoma brucei lines infect humans whereas others do not because the parasites are lysed by human serum. We have developed a robust, quantitative in vitro assay based on differential uptake of fluorescent dyes by live and dead trypanosomes to quantify the extent and kinetics of killing by human serum. This method has been used to discriminate between three classes of human serum resistance; sensitive, resistant and intermediate. TREU 927/4, the parasite used for the T. brucei genome project, is intermediate. The phenotype is expressed in both bloodstream and metacyclic forms, is stably expressed during chronic infections and on cyclical transmission through tsetse flies. Trypanosomes of intermediate phenotype are distinguished from sensitive populations of cells by the slower rate of lysis and by the potential to become fully resistant to killing by human serum as a result of selection or long-term serial passaging in mice and to pass on full resistance phenotype to its progeny in a genetic cross. The sra gene has been shown previously to determine human serum resistance in T. brucei but screening for the presence and expression of this gene indicated that it is not responsible for the human serum resistance phenotype in the trypanosome lines that we have examined, indicating an alternative mechanism for HSR exists in these stocks. Examination of the inheritance of the phenotype in F1 hybrids for both bloodstream and metacyclic stages from two genetic crosses demonstrated that the phenotype is co-inherited in both life cycle stages in a manner consistent with being a Mendelian trait, determined by only one or a few genes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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Human infectivity trait in Trypanosoma brucei: stability, heritability and relationship to sra expression

et al. 2004

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“…Procyclic culture forms (PCF) of T. b. brucei 427.01, T. b. gambiense U2 [18], T. b. rhodesiense ViTat 1.1 [19], and T. congolense IL3000 [20] were derived from their corresponding BSF by transformation at 27°C [21]. Tsetse transmissible T. b. brucei TSW 196 PCF [22] were obtained from the Liverpool School of Tropical Medicine. All PCF were cultured in MEM/10% FBS as described [20],[23].…”

Section: Methodsmentioning

confidence: 99%

Killing of Trypanosomatid Parasites by a Modified Bovine Host Defense Peptide, BMAP-18

et al. 2009

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BackgroundTropical diseases caused by parasites continue to cause socioeconomic devastation that reverberates worldwide. There is a growing need for new control measures for many of these diseases due to increasing drug resistance exhibited by the parasites and problems with drug toxicity. One new approach is to apply host defense peptides (HDP; formerly called antimicrobial peptides) to disease control, either to treat infected hosts, or to prevent disease transmission by interfering with parasites in their insect vectors. A potent anti-parasite effector is bovine myeloid antimicrobial peptide-27 (BMAP-27), a member of the cathelicidin family. Although BMAP-27 is a potent inhibitor of microbial growth, at higher concentrations it also exhibits cytotoxicity to mammalian cells. We tested the anti-parasite activity of BMAP-18, a truncated peptide that lacks the hydrophobic C-terminal sequence of the BMAP-27 parent molecule, an alteration that confers reduced toxicity to mammalian cells.Methodology/Principal FindingsBMAP-18 showed strong growth inhibitory activity against several species and life cycle stages of African trypanosomes, fish trypanosomes and Leishmania parasites in vitro. When compared to native BMAP-27, the truncated BMAP-18 peptide showed reduced cytotoxicity on a wide variety of mammalian and insect cells and on Sodalis glossindius, a bacterial symbiont of the tsetse vector. The fluorescent stain rhodamine 123 was used in immunofluorescence microscopy and flow cytometry experiments to show that BMAP-18 at low concentrations rapidly disrupted mitochondrial potential without obvious alteration of parasite plasma membranes, thus inducing death by apoptosis. Scanning electron microscopy revealed that higher concentrations of BMAP-18 induced membrane lesions in the parasites as early as 15 minutes after exposure, thus killing them by necrosis. In addition to direct killing of parasites, BMAP-18 was shown to inhibit LPS-induced secretion of tumour necrosis factor alpha (TNF-α), a cytokine that is associated with inflammation and cachexia (wasting) in sleeping sickness patients. As a prelude to in vivo applications, high affinity antibodies to BMAP-18 were produced in rabbits and used in immuno-mass spectrometry assays to detect the intact peptide in human blood and plasma.Conclusions/SignificanceBMAP-18, a truncated form of the potent antimicrobial BMAP-27, showed low toxicity to mammalian cells, insect cells and the tsetse bacterial symbiont Sodalis glossinidius while retaining an ability to kill a variety of species and life cycle stages of pathogenic kinetoplastid parasites in vitro. BMAP-18 also inhibited secretion of TNF-α, an inflammatory cytokine that plays a role in the cachexia associated with African sleeping sickness. These findings support the idea that BMAP-18 should be explored as a candidate for therapy of economically important trypanosome-infected hosts, such as cattle, fish and humans, and for paratransgenic expression in Sodalis glossinidius, a bacterial symbiont in the tsetse vector, a...

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“…A single Glossina sp lab strain is most unlikely to be representative of the species over much of its geographic range and multiple, independently derived lab strains from diverse natural populations are unavailable. Second, even though HAT epidemics are typically of one trypanosome genotype, i.e., clonal (but see Agbo et al, 2003 for contrary evidence), natural populations of T. brucei s.l. are genetically differentiated in ways that remain largely unknown.…”

Section: Vector-parasite-mammalian Co-adaptationsmentioning

confidence: 99%

Tsetse flies: Genetics, evolution, and role as vectors

Krafsur

2009

Infection, Genetics and Evolution

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Tsetse flies (Diptera: Glossinidae) are an ancient taxon of one genus, Glossina, and limited species diversity. All are exclusively haematophagous and confined to sub-Saharan Africa. The Glossina are the principal vectors of African trypanosomes Trypanosoma sp. (Kinetoplastida: Trypanosomatidae) and as such, are of great medical and economic importance. Clearly tsetse flies and trypanosomes are coadapted and evolutionary interactions between them are manifest. Numerous clonally reproducing strains of Trypanosoma sp. exist and their genetic diversities and spatial distributions are inadequately known. Here I review the breeding structures of the principle trypanosome vectors, G. morsitans s.l., G. pallidipes, G. palpalis s.l. and G. fuscipes fuscipes. All show highly structured populations among which there is surprisingly little detectable gene flow. Rather less is known of the breeding structure of T. brucei sensu lato vis à vis their vector tsetse flies but many genetically differentiated strains exist in nature. Genetic recombination in Trypanosoma via meiosis has recently been demonstrated in the laboratory thereby furnishing a mechanism of strain differentiation in addition to that of simple mutation. Spatially and genetically representative sampling of both trypanosome species and strains and their Glossina vectors is a major barrier to a comprehensive understanding of their mutual relationships. G. morsitans s.l., G. pallidipes, G. palpalis s.l. and G. fuscipes fuscipes. All show highly structured populations among which there is surprisingly little detectable gene flow. Rather less is known of the breeding structure of T. brucei sensu lato vis à vis their vector tsetse flies but many genetically differentiated strains exist in nature. Genetic recombination in Trypanosoma via meiosis has recently been demonstrated in the laboratory thereby furnishing a mechanism of strain differentiation in addition to that of simple mutation. Spatially and genetically representative sampling of both trypanosome species and strains and their Glossina vectors is a major barrier to a comprehensive understanding of their mutual relationships.

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Population genetic structure and cladistic analysis of Trypanosoma brucei isolates

Cited by 7 publications

References 31 publications

Human infectivity trait in Trypanosoma brucei: stability, heritability and relationship to sra expression

Human infectivity trait in Trypanosoma brucei: stability, heritability and relationship to sra expression

Killing of Trypanosomatid Parasites by a Modified Bovine Host Defense Peptide, BMAP-18

Tsetse flies: Genetics, evolution, and role as vectors

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