The role of transferrin-receptor variation in the host range of Trypanosoma brucei

Bitter, Wilbert; Gerrits, Herlinde; Kieft, Rudo; Borst, Piet

doi:10.1038/35166

Cited by 137 publications

(125 citation statements)

References 26 publications

(12 reference statements)

Supporting

Mentioning

124

Contrasting

Order By: Relevance

“…This method of switching accesses a relatively small pool of 20 VSG genes. However, recent evidence indicates that the different VSG expression sites each con- tain genes encoding receptor proteins that are optimized for different hosts (Bitter et al 1998). This could mean that in situ switches are important during the establishment of the trypanosome in a new host species.…”

mentioning

confidence: 99%

Mechanisms Mediating Antigenic Variation in Trypanosoma brucei

Rudenko

1999

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

Antigenic variation in MECHANISMS OF ANTIGENIC VARIATIONAfrican trypanosomes are effective pathogens, as they can establish chronic infections in man and his lifestock, despite being fully exposed to periodic assault by the immune system. Their survival strategy is based on ensuring that at a low frequency, trypanosomes arise which have changed the epitopes exposed on their surface. This exchangeable surface coat is a homogeneous layer composed of a single variant surface glycoprotein (VSG). As each individual trypanosome encodes up to a thousand VSG genes, and is capable of making chimaeric new ones, the potential for variation during a protracted infection is endless.Intense research by many laboratories in the eighties laid the basis for what is known about the main mechanisms of VSG switching in bloodstream form Trypanosoma brucei. Any given VSG coat is encoded by a single VSG gene transcribed in an expression site located at the ends of certain chromosomes. As there are 20 bloodstream form VSG expression sites, one way of switching is simply to silence the active expression site and activate a new one (an in situ switch). This method of switching accesses a relatively small pool of 20 VSG genes. However, recent evidence indicates that the different VSG expression sites each con- tain genes encoding receptor proteins that are optimized for different hosts (Bitter et al. 1998). This could mean that in situ switches are important during the establishment of the trypanosome in a new host species.VSG switching can also be mediated by DNA rearrangements like gene conversions or telomere exchange. Gene conversions access the largest pool of VSG genes (virtually all of them). A silent VSG gene is copied and inserted into the active expression site, replacing the old VSG gene. Alternatively, trypanosomes can switch via telomere exchange, whereby a silent VSG gene at a chromosome end is flipped into the active VSG expression site. Recent overviews of antigenic variation are Donelson (1995), Vanhamme and Pays (1995), Borst et al. (1996), Cross (1996, Barry (1997), Rudenko et al. (1998b).The problem with studying antigenic variation in the field has been that all of these mechanisms are operating at the same time, and antigenic populations of parasites within an animal are normally not monoclonal. The 20 VSG expression sites are highly similar with each other, with only the VSG gene as a unique marker. Once the VSG gene has been switched a few times, it can be very difficult to reconstruct how this has happened. Due to the polyclonal nature of the infection, it is also impossible to prove that trypanosomes present in various peaks are sequentially derived from each other. In contrast, single relapse experiments with laboratory strains are a highly simplified model system, which should give us insights into how antigenic variation is mediated in field strains.

show abstract

mentioning

confidence: 99%

Mechanisms Mediating Antigenic Variation in Trypanosoma brucei

Rudenko

1999

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

show abstract

“…The ESAG6 and ESAG7 subunits contain VSG-like N-terminal domains that facilitate packing within the VSG surface coat in the flagellar pocket and variable C-terminal sequences with differing affinities for mammalian transferrins (55). Growth of trypanosomes in different sera can select for VSG ES switching and results in the expression of different Tf-Rs (5,15). A correlation to the relative transferrin binding affinity of the expressed trypanosome Tf-R and the host transferrin has been made previously (15,71).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2006

View full text Add to dashboard Cite

“…However, Witola et al (2005) and Mekata et al (2009) reported that ESAG6/7 gene only showed sequence difference about 1-10%. Despite its small difference, but its reported to cause affinity difference of different transferrin host (Bitter et al 1998). In contrast to the T. evansi isolates from Thailand, Indonesian T. evansi isolates tend to be homogeneous on the transferring binding site located on box II and III (Figure 3) (Salmon et al 1997).…”

Section: Sequencing Analysis Of Esag6/7 T Evansi Genementioning

confidence: 95%

“…That two ESAG only showed the different of a sequence about 1-10% (Witola et al 2005;Mekata et al 2009). Despite that small difference, it was reported to be able to cause affinity difference of transferrin host (Bitter et al 1998;Steverding et al 1995). Bitter et al (1998) reported that natural variability of ESAG6/7 might affect the ability of trypanosome to take Tf molecule from various species of Mammalia as host.…”

Section: Introductionmentioning

confidence: 99%

“…Despite that small difference, it was reported to be able to cause affinity difference of transferrin host (Bitter et al 1998;Steverding et al 1995). Bitter et al (1998) reported that natural variability of ESAG6/7 might affect the ability of trypanosome to take Tf molecule from various species of Mammalia as host. Isobe et al (2003) and Witola et al (2005) reported that on Trypanosoma equiperdum, where this parasite only infected horse, has known as ESAG6 gene, which was less diverse compared to T. brucei and T. evansi infecting wide range host (Isobe et al 2003).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genetic variability of ESAG6/7 gene Trypanosoma evansi

Sawitri¹,

Wardhana²

2018

JITV

View full text Add to dashboard Cite

ABSTRAKSawitri DH, Wardhana AH. 2017. Variabilitas genetik dari gen ESAG 6/7 Isolat T. evansi. JITV 22(1): 38-50. DOI: http://dx.doi.org/10.14334/jitv.v22i1.1638Trypanosoma evansi (T. evansi) sebagai agen penyakit Sura merupakan salah satu penyakit parasitik penting untuk diperhatikan karena dapat menimbulkan kerugian ekonomi yang sangat besar di Indonesia. Parasit ini memerlukan zat besi untuk fase propagasi yang diperoleh dari pejamu melalui reseptor transferrin (Tf) yang dikode oleh Expression Site Associated Genees (ESAGs). ESAG6/7 dilaporkan mengkode reseptor transferrin pada afinitas yang berbeda pada pejamu yang berbeda.Adanya perbedaan patogeneitas T. evansi diduga menyebabkan variabilitas pada gene ESAG 6/7. Penelitian ini bertujuan untuk melihat variabilitas gene ESAG6 T. evansi dengan virulensi yang berbeda pada mencit. Penelitian ini dilakukan dengan 2 tahap yaitu uji patogeneitas T. evansi pada mencit dan analisis sekuen gene ESAG6/7. Uji patogeneitas dilakukan dengan melihat median lama hidup mencit setelah masing-masing kelompok diinfeksi dengan 25 T. evansi asal kerbau dari berbagai kondisi geografi. Hasil penelitian uji patogeneitas menunjukkan adanya perbedaan virulensi pada 25 isolat T.evansi pada mencit. Trypanosoma evansi as an agent of Surra is one of the crucial parasitic diseases that cause great economic losses in Indonesia. These parasites need iron for growth and propagation phase which is obtained by receptor-mediated uptake of host transferin. The transferrin receptors are encoded by Expression Site Associated Genees (ESAGs). ESAG6/7 encodes transferrin receptors which reported have different affinities of a different host. The distinction of T. evansi pathogenicity is supposed to cause variability in the ESAG6/7 gene. This research was aimed to investigate the variability of genes ESAG6/7 T. evansi with different virulence in mice. This research was conducted in two steps: bioassay pathogeneicity in mice and analysis of ESAG6/7 gene sequences. The median survival time of mice was investigated after each group of mice infected by 25 T. evansi isolates from buffaloes where its geographically differ. The test results showed a difference of pathogenic virulence on 25 T. evansi isolates in mice. Sequence analysis of the ESAG6/7 gene from 25 T. evansi isolates origin from Indonesia tended to be homogeneous on the transferrin binding site but there was variability in the hypervariable site. These changes are able to separate high and low virulence of the T. evansi isolates. Phylogenetic tree analysis was formed 11 clades of 25 T. evansi. High virulence T. evansi was included in clades 7 and 10, while low virulence T. evansi was included in clade 5 and 11 and the moderate virulence was divided into those four clades.

show abstract

The role of transferrin-receptor variation in the host range of Trypanosoma brucei

Cited by 137 publications

References 26 publications

Mechanisms Mediating Antigenic Variation in Trypanosoma brucei

Mechanisms Mediating Antigenic Variation in Trypanosoma brucei

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

Genetic variability of ESAG6/7 gene Trypanosoma evansi

Contact Info

Product

Resources

About