imprint:
Springer Science and Business Media LLC, 2019
Published in:Communications Biology
Language:
English
DOI:
10.1038/s42003-019-0429-z
ISSN:
2399-3642
Origination:
Footnote:
Description:
<jats:title>Abstract</jats:title><jats:p>PfEMP1 (erythrocyte membrane protein 1) adhesins play a pivotal role in the pathophysiology of falciparum malaria, by mediating sequestration of <jats:italic>Plasmodium falciparum</jats:italic>-infected erythrocytes in the microvasculature. PfEMP1 variants are expressed by <jats:italic>var</jats:italic> genes and are presented on membrane elevations, termed knobs. However, the organization of PfEMP1 on knobs is largely unclear. Here, we use super-resolution microscopy and genetically altered parasites expressing a modified <jats:italic>var2cs</jats:italic>a gene in which the coding sequence of the photoactivatable mEOS2 was inserted to determine the number and distribution of PfEMP1 on single knobs. The data were verified by quantitative fluorescence-activated cell sorting analysis and immuno-electron microscopy together with stereology methods. We show that knobs contain 3.3 ± 1.7 and 4.3 ± 2.5 PfEMP1 molecules, predominantly placed on the knob tip, in parasitized erythrocytes containing wild type and sickle haemoglobin, respectively. The ramifications of our findings for cytoadhesion and immune evasion are discussed.</jats:p>