DNA metabolism and genetic diversity in Trypanosomes

Machado, Carlos Renato; Augusto-Pinto, Luiz; McCulloch, Richard; Teixeira, Santuza Maria Ribeiro

doi:10.1016/j.mrrev.2005.05.001

Cited by 38 publications

(32 citation statements)

References 139 publications

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“…Another strategy used by T. cruzi is antigen variation in face of an immune response aiming at host protection. Such modifications are also related to morphological variations in the parasite biological cycle, which involves various antigens in their different phases [41]. Additionally, the T. cruzi's genome is highly complex and repetitive, which facilitates genetic recombination and enhancement of devices that allow the parasite to escape the attacks from the host immune system [42].…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, the T. cruzi's genome is highly complex and repetitive, which facilitates genetic recombination and enhancement of devices that allow the parasite to escape the attacks from the host immune system [42]. At the same time, T.cruzi produces plenty of surface protein variants that enable parasite to avoid antibodies [41]. These are mechanisms that can alter the recognition of such proteins by antibodies, leading to variations in the responses to serological tests of the same individual at different moments.…”

Section: Discussionmentioning

confidence: 99%

“…These are mechanisms that can alter the recognition of such proteins by antibodies, leading to variations in the responses to serological tests of the same individual at different moments. Genetic diversity of T. cruzi lineages infecting different individuals may be responsible for the differences in the titles of antibodies found as well as for clinical manifestations in the chronic phase of Chagas disease [41,43,44].…”

Section: Discussionmentioning

confidence: 99%

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Definition of a diagnostic routine in individuals with inconclusive serology for chagas disease

Picka¹,

Meira²,

Carvalho³

et al. 2007

Braz J Infect Dis

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Despite the existence of highly sensitive tests, inconclusive serological results are frequent in chronic chagasic infection. This study aimed to define a diagnostic conduct for 30 individuals with inconclusive serology (G3) for chagasic infection assisted at the Outpatient Unit for Infectious and Parasitic Diseases of the Botucatu School of Medicine. Twenty-one individuals with negative serology (G1) and 33 with positive serology (G2) were also studied. Serological methods ELISA, HAI, IFI and immunoblotting TESA-cruzi were used for G1, G2 and G3, and parasitological methods xenodiagnosis, hemoculture and PCR-LIT were used for G2 and G3 individuals. ELISA, HAI and IFI were performed in 5 different blood samples in G2 and G3. TESA-cruzi was carried out only once in G1, G2 and G3 and, since it is the most sensitive, it was utilized as standard. In G3, positivity for ELISA reached 86% in the fifth blood sample; the ELISA+HAI+IFI combination showed a maximum of 44.8% in the second sample; and TESA-cruzi, 76% in one single sample. Xenodiagnosis positivity was 9.4%; hemoculture showed 15.2%; and PCR-LIT exhibited 22% positivity in G2. Nevertheless, in G3, positivity percentage was 3.4% for xenodiagnosis, 6.7% for PCR-LIT, and no positive result was found for hemoculture. In G3, PCR-LIT resolved one case which was still inconclusive according to serology tests. In order to define inconclusive diagnoses, the results suggest the combined use of ELISA+HAI+IFI in 2 blood samples, decreasing the occurrence of false positive/negative results. If results remain inconclusive, the performance of TESA-cruzi and PCR-LIT, if necessary, is recommended.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Definition of a diagnostic routine in individuals with inconclusive serology for chagas disease

Picka¹,

Meira²,

Carvalho³

et al. 2007

Braz J Infect Dis

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“…1b), there are three distinct clusters formed by (a) the highly expressed genes (red), (b) the variant surface glycoproteins or VSG genes (blue) and (c) the rest of genes (black). In T. brucei, the key to survival is a huge repertoire of antigenically distinct VSGs, expression patterns of which change periodically during a chronic infection [16]. Switching the expressed VSG allows the parasite population to escape immune killing mediated by the antibodies produced against the previously expressed VSG [17].…”

Section: Distinct Codon Usage In Variant Surface Glycoproteinsmentioning

confidence: 99%

Comparative codon and amino acid composition analysis of Tritryps‐conspicuous features of Leishmania major

Chanda¹,

Pan²,

Saha³

et al. 2007

FEBS Letters

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Comparative analyses of codon/amino acid usage in Leishmania major, Trypanosoma brucei and Trypanosoma cruzi reveal that gene expressivity and GC-bias play key roles in shaping the gene composition of all three parasites, and protein composition of L. major only. In T. brucei and T. cruzi, the major contributors to the variation in protein composition are hydropathy and/or aromaticity. Principle of Cost Minimization is followed by T. brucei, disregarded by T. cruzi and opposed by L. major. Slowly evolving highly expressed gene-products of L. major bear signatures of relatively AT-rich ancestor, while faster evolution under GC-bias has characterized the lowly expressed genes of the species by higher GC 12 -content.

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“…Since DNA rearrangements play a crucial role in the diversification of important surface antigens, the availability and preferential use of different DNA repair pathways should be considered a key component of the process of antigenic variation. While DNA recombination and repair have long been considered to be intimately tied to antigenic variation in organisms like African trypanosomes (9,10), they are just recently becoming appreciated for malaria parasites. The unique complement of repair pathways present in malaria parasites are thus likely to be tied to pathogenesis as well as the generation of antigenic diversity.…”

Section: Introductionmentioning

confidence: 99%

Recombination and Diversification of the Variant Antigen Encoding Genes in the Malaria Parasite Plasmodium falciparum

Kirkman

Deitsch

2014

Microbiol Spectr

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The most severe form of human malaria is caused by the protozoan parasite Plasmodium falciparum. These parasites invade and replicate within the circulating red blood cells of infected individuals leading to numerous disease manifestations, including severe anemia, altered circulation, and tissue inflammation. Malaria parasites are also known for their ability to maintain a chronic infection through antigenic variation, the ability to systematically alter the antigens displayed on the surface of infected cells and thereby avoid clearance by the host's antibody response. The genome of P. falciparum includes several large, multicopy gene families that encode highly variable forms of the surface proteins that are the targets of host immunity. Alterations in expression of genes within these families are responsible for antigenic variation. This process requires the continuous generation of new antigenic variants within these gene families, and studies have shown that new variants arise through extensive recombination and gene conversion events between family members. Malaria parasites possess an unusual complement of DNA repair pathways, thus the study of recombination between variant antigen encoding genes provides a unique view into the evolution of mobile DNA in an organism distantly related to the more closely studied model eukaryotes.

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DNA metabolism and genetic diversity in Trypanosomes

Cited by 38 publications

References 139 publications

Definition of a diagnostic routine in individuals with inconclusive serology for chagas disease

Definition of a diagnostic routine in individuals with inconclusive serology for chagas disease

Comparative codon and amino acid composition analysis of Tritryps‐conspicuous features of Leishmania major

Recombination and Diversification of the Variant Antigen Encoding Genes in the Malaria Parasite Plasmodium falciparum

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