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Differential var gene expression in the organs of patients dying of falciparum malaria.

Montgomery J, Mphande FA, Berriman M, Pain A, Rogerson SJ, Taylor TE, Molyneux ME, Craig A - Mol. Microbiol. (2007)

Bottom Line: Despite up to 102 different var genes being expressed by P. falciparum populations in a single host, only one to two of these genes were expressed at high levels in the brains and hearts of these patients.These major var types differed between organs.However, identical var types were expressed in the brains of multiple patients from a single malaria season.

View Article: PubMed Central - PubMed

Affiliation: Malawi-Liverpool-Wellcome Programme of Clinical Tropical Research, College of Medicine, Blantyre, Malawi. jmontgomery@mlw.medcol.mw

ABSTRACT
Sequestration of parasitized erythrocytes in the microcirculation of tissues is thought to be important in the pathogenesis of severe falciparum malaria. A major variant surface antigen, var/Plasmodium falciparum erythrocyte membrane protein 1, expressed on the surface of the infected erythrocyte, mediates cytoadherence to vascular endothelium. To address the question of tissue-specific accumulation of variant types, we used the unique resource generated by the clinicopathological study of fatal paediatric malaria in Blantyre, Malawi, to analyse var gene transcription in patients dying with falciparum malaria. Despite up to 102 different var genes being expressed by P. falciparum populations in a single host, only one to two of these genes were expressed at high levels in the brains and hearts of these patients. These major var types differed between organs. However, identical var types were expressed in the brains of multiple patients from a single malaria season. These results provide the first evidence of organ-specific accumulation of P. falciparum variant types and suggest that parasitized erythrocytes can exhibit preferential binding in the body, supporting the hypothesis of cytoadherence-linked pathogenesis.

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Frequency of var types in the organs of paediatric malaria patients. Each graph represents one patient (labelled above with final diagnosis in parentheses) with organs denoted by shading. var types are listed on the y-axis by accession number and the frequency of cloning is adjusted for the number of complete sequences analysed from each organ. Single copy var types are represented together and labelled 1× var.
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fig01: Frequency of var types in the organs of paediatric malaria patients. Each graph represents one patient (labelled above with final diagnosis in parentheses) with organs denoted by shading. var types are listed on the y-axis by accession number and the frequency of cloning is adjusted for the number of complete sequences analysed from each organ. Single copy var types are represented together and labelled 1× var.

Mentions: Ninety-six products were cloned from each reaction, sequenced and aligned, with comparable frequencies of individual var types observed in the duplicate reactions. Sequences from the pilot study were also included in analyses. A total of 133–202 clones were obtained from each organ sample with 2020 clones overall. Hereafter, ‘clone’ will refer to each sequenced RT-PCR product, and ‘type’ will refer to each different DBL1α sequence identified. A median of 26 (range 11–49) different var types were amplified from each organ of the three patients. Figure 1 illustrates the cloning frequency of individual var types and the overlap between organs and patients. Half of the 248 var types were detected a single time in one organ only, accounting for only 6% of clones examined. All other var types were cloned more than once from a single organ or were detected in multiple organs and/or cases. The single copy clones were grouped together in Fig. 1 (1× var) and excluded from motif analysis.


Differential var gene expression in the organs of patients dying of falciparum malaria.

Montgomery J, Mphande FA, Berriman M, Pain A, Rogerson SJ, Taylor TE, Molyneux ME, Craig A - Mol. Microbiol. (2007)

Frequency of var types in the organs of paediatric malaria patients. Each graph represents one patient (labelled above with final diagnosis in parentheses) with organs denoted by shading. var types are listed on the y-axis by accession number and the frequency of cloning is adjusted for the number of complete sequences analysed from each organ. Single copy var types are represented together and labelled 1× var.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2170262&req=5

fig01: Frequency of var types in the organs of paediatric malaria patients. Each graph represents one patient (labelled above with final diagnosis in parentheses) with organs denoted by shading. var types are listed on the y-axis by accession number and the frequency of cloning is adjusted for the number of complete sequences analysed from each organ. Single copy var types are represented together and labelled 1× var.
Mentions: Ninety-six products were cloned from each reaction, sequenced and aligned, with comparable frequencies of individual var types observed in the duplicate reactions. Sequences from the pilot study were also included in analyses. A total of 133–202 clones were obtained from each organ sample with 2020 clones overall. Hereafter, ‘clone’ will refer to each sequenced RT-PCR product, and ‘type’ will refer to each different DBL1α sequence identified. A median of 26 (range 11–49) different var types were amplified from each organ of the three patients. Figure 1 illustrates the cloning frequency of individual var types and the overlap between organs and patients. Half of the 248 var types were detected a single time in one organ only, accounting for only 6% of clones examined. All other var types were cloned more than once from a single organ or were detected in multiple organs and/or cases. The single copy clones were grouped together in Fig. 1 (1× var) and excluded from motif analysis.

Bottom Line: Despite up to 102 different var genes being expressed by P. falciparum populations in a single host, only one to two of these genes were expressed at high levels in the brains and hearts of these patients.These major var types differed between organs.However, identical var types were expressed in the brains of multiple patients from a single malaria season.

View Article: PubMed Central - PubMed

Affiliation: Malawi-Liverpool-Wellcome Programme of Clinical Tropical Research, College of Medicine, Blantyre, Malawi. jmontgomery@mlw.medcol.mw

ABSTRACT
Sequestration of parasitized erythrocytes in the microcirculation of tissues is thought to be important in the pathogenesis of severe falciparum malaria. A major variant surface antigen, var/Plasmodium falciparum erythrocyte membrane protein 1, expressed on the surface of the infected erythrocyte, mediates cytoadherence to vascular endothelium. To address the question of tissue-specific accumulation of variant types, we used the unique resource generated by the clinicopathological study of fatal paediatric malaria in Blantyre, Malawi, to analyse var gene transcription in patients dying with falciparum malaria. Despite up to 102 different var genes being expressed by P. falciparum populations in a single host, only one to two of these genes were expressed at high levels in the brains and hearts of these patients. These major var types differed between organs. However, identical var types were expressed in the brains of multiple patients from a single malaria season. These results provide the first evidence of organ-specific accumulation of P. falciparum variant types and suggest that parasitized erythrocytes can exhibit preferential binding in the body, supporting the hypothesis of cytoadherence-linked pathogenesis.

Show MeSH
Related in: MedlinePlus