Switching trypanosome coats: what's in the wardrobe?

Taylor, Jamie; Rudenko, Gloria

doi:10.1016/j.tig.2006.08.003

Cited by 171 publications

(135 citation statements)

References 49 publications

Supporting

Mentioning

133

Contrasting

Unclassified

Order By: Relevance

“…They proliferate as extracellular parasites in the bloodstream of their mammalian host and can, later on, cross the blood-brain barrier to provoke severe neurological symptoms that are fatal in the absence of treatment . Trypanosomes evade the host immune response by a sophisticated process of antigenic variation involving a dense surface coat of a single type of protein called variant surface glycoprotein (Berriman et al, 2005;Cross, 1975;Taylor and Rudenko, 2006). There is no vaccine and treatments are difficult to administer in rural areas and can provoke severe side effects .…”

Section: Introductionmentioning

confidence: 99%

A new asymmetric division contributes to the continuous production of infective trypanosomes in the tsetse fly

et al. 2012

View full text Add to dashboard Cite

SUMMARYAfrican trypanosomes are flagellated protozoan parasites that cause sleeping sickness and are transmitted by the bite of the tsetse fly. To complete their life cycle in the insect, trypanosomes reach the salivary glands and transform into the metacyclic infective form. The latter are expelled with the saliva at each blood meal during the whole life of the insect. Here, we reveal a means by which the continuous production of infective parasites could be ensured. Dividing trypanosomes present in the salivary glands of infected tsetse flies were monitored by live video-microscopy and by quantitative immunofluorescence analysis using molecular markers for the cytoskeleton and for surface antigens. This revealed the existence of two distinct modes of trypanosome proliferation occurring simultaneously in the salivary glands. The first cycle produces two equivalent cells that are not competent for infection and are attached to the epithelium. This mode of proliferation is predominant at the early steps of infection, ensuring a rapid colonization of the glands. The second mode is more frequent at later stages of infection and involves an asymmetric division. It produces a daughter cell that matures into the infective metacyclic form that is released in the saliva, as demonstrated by the expression of specific molecular markers -the calflagins. The levels of these calcium-binding proteins increase exclusively in the new flagellum during the asymmetric division, showing the commitment of the future daughter cell to differentiation. The coordination of these two alternative cell cycles contributes to the continuous production of infective parasites, turning the tsetse fly into an efficient and long-lasting vector for African trypanosomes.

show abstract

Section: Introductionmentioning

confidence: 99%

A new asymmetric division contributes to the continuous production of infective trypanosomes in the tsetse fly

et al. 2012

View full text Add to dashboard Cite

show abstract

“…The strategy of varying antigen presentation over time is found in diverse pathogens, including protozoa, viruses, helminths and bacteria (Barbour, 1987;Centurion-Lara et al, 2004;Diamond, 2003;Kline et al, 2003;Taylor & Rudenko, 2006;Zhang et al, 1997). In order to produce variant antigens, the pathogen typically can produce variant genes de novo (e.g.…”

Section: Introductionmentioning

confidence: 99%

Antigen variability in Anaplasma phagocytophilum during chronic infection of a reservoir host

et al. 2012

View full text Add to dashboard Cite

“…Antigenic variants are generated by gene conversion in which an intact hypervariable region (HVR) or an HVR oligonucleotide segment is recombined from nonexpressed chromosomal loci into the major surface protein-2 (Msp2) expression site (9,10). This mechanism is very similar to that used by African trypanosomes in which the complete (or nearly complete) variable surface glycoprotein (VSG) coding sequences or oligonucleotide segments are recombined into an expression site to generate a new VSG variant (11). Importantly, A. marginale has a relatively small genome (1/20th the size of Trypanosoma brucei), facilitating the sequencing of the complete repertoire of chromosomal msp2 donor alleles in each of multiple strains (9,12,13), data required to test the hypothesis but not yet available for other highly antigenically variable vector-borne pathogens such as Babesia, Plasmodium, and Trypanosoma (14 -17).…”

mentioning

confidence: 99%

Superinfection as a driver of genomic diversification in antigenically variant pathogens

Futse

Brayton

Dark

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

A new pathogen strain can penetrate an immune host population only if it can escape immunity generated against the original strain. This model is best understood with influenza viruses, in which genetic drift creates antigenically distinct strains that can spread through host populations despite the presence of immunity against previous strains. Whether this selection model for new strains applies to complex pathogens responsible for endemic persistent infections, such as anaplasmosis, relapsing fever, and sleeping sickness, remains untested. These complex pathogens undergo rapid within-host antigenic variation by using sets of chromosomally encoded variants. Consequently, immunity is developed against a large repertoire of variants, dramatically changing the scope of genetic change needed for a new strain to evade existing immunity and establish coexisting infection, termed strain superinfection. Here, we show that the diversity in the alleles encoding antigenic variants between strains of a highly antigenically variant pathogen was equal to the diversity within strains, reflecting equivalent selection for variants to overcome immunity at the host population level as within an individual host. This diversity among strains resulted in expression of nonoverlapping variants that allowed a new strain to evade immunity and establish superinfection. Furthermore, we demonstrated that a single distinct allele allows strain superinfection. These results indicate that there is strong selective pressure to increase the diversity of the variant repertoire beyond what is needed for persistence within an individual host and provide an explanation, competition at the host population level, for the large genomic commitment to variant gene families in persistent pathogens.antigenic variation ͉ genomic diversity ͉ population immunity

show abstract

Switching trypanosome coats: what's in the wardrobe?

Cited by 171 publications

References 49 publications

A new asymmetric division contributes to the continuous production of infective trypanosomes in the tsetse fly

A new asymmetric division contributes to the continuous production of infective trypanosomes in the tsetse fly

Antigen variability in Anaplasma phagocytophilum during chronic infection of a reservoir host

Superinfection as a driver of genomic diversification in antigenically variant pathogens

Contact Info

Product

Resources

About