Abstract
Merozoite invasion of host red blood cells (RBCs) is essential for survival of the human malaria parasite Plasmodium falciparum. Proteins involved with RBC binding and invasion are secreted from dual-club shaped organelles at the apical tip of the merozoite called the rhoptries. Here we characterise P. falciparum Cytosolically Exposed Rhoptry Leaflet Interacting protein 2 (PfCERLI2), as a rhoptry bulb protein that is essential for merozoite invasion. Phylogenetic analyses show that cerli2 arose through an ancestral gene duplication of cerli1. We show that PfCERLI2 is essential for blood-stage growth and localises to the cytosolic face of the rhoptry bulb. Inducible knockdown of PfCERLI2 led to a proportion of merozoites failing to invade and was associated with elongation of the rhoptry organelle during merozoite development and inhibition of rhoptry antigen processing. These findings identify PfCERLI2 as a protein that has key roles in rhoptry biology during merozoite invasion.
| Original language | English |
|---|---|
| Article number | 121 |
| Number of pages | 17 |
| Journal | Communications Biology |
| Volume | 5 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Dec 2022 |
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Cell biological analysis reveals an essential role for Pfcerli2 in erythrocyte invasion by malaria parasites. / Liffner, Benjamin; Balbin, Juan Miguel; Shami, Gerald J. et al.
In: Communications Biology, Vol. 5, No. 1, 121, 12.2022.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Cell biological analysis reveals an essential role for Pfcerli2 in erythrocyte invasion by malaria parasites
AU - Liffner, Benjamin
AU - Balbin, Juan Miguel
AU - Shami, Gerald J.
AU - Siddiqui, Ghizal
AU - Strauss, Jan
AU - Frölich, Sonja
AU - Heinemann, Gary K.
AU - Edwards, Ella May
AU - Alder, Arne
AU - Wichers, Jan Stephan
AU - Creek, Darren J.
AU - Tilley, Leann
AU - Dixon, Matthew W.A.
AU - Gilberger, Tim Wolf
AU - Wilson, Danny W.
N1 - Funding Information: We thank Prof. Alan Cowman for provision of RON4, EBA175 and GAP45 antibodies, A/Prof. Wai-Hong Tham for RH4 antibodies, Dr. Matt Dixon for GAPDH and ERC antibodies. We also thank Dr. Paul Gilson for the PTEX150 HAGlmS transfection vector, MSP1-19 and EXP2 antibodies. Fluorescence imaging was performed at Adelaide Microscopy (The University of Adelaide) and the Centre for Cancer Biology (UniSA). Electron microscopy was performed at the Ian Holmes Imaging Centre, Bio21, The University of Melbourne (www.microscopy.unimelb.edu.au). For provision of the SLI-TGD vector, we thank Dr. Tobias Spielmann. We thank Dr. Brad Sleebs for Compound 1. We thank the Australian Red Cross Blood Bank for the provision of human blood that was collected with informed consent of the donors. We thank the VEuPathDB team, as access to their database enabled much of this research. This work was supported by funding from the NHMRC (Project Grant APP1143974, D.W.W.), University of Adelaide Beacon Fellowship and Hospital Research Foundation Fellowship (D.W.W.), DAAD/Universities Australia joint research co-operation scheme (T.G., D.W.W., B.L., J.B.), Australian Government Research Training Program Scholarship (B.L., J.B.), South Australian Commonwealth Scholarship (B.L.), DFG BA5213/3-1 (J.S.W.) and J?rgen Manchot-Stiftung fellowship (A.A.). Funding Information: We thank Prof. Alan Cowman for provision of RON4, EBA175 and GAP45 antibodies, A/Prof. Wai-Hong Tham for RH4 antibodies, Dr. Matt Dixon for GAPDH and ERC antibodies. We also thank Dr. Paul Gilson for the PTEX150 transfection vector, MSP1-19 and EXP2 antibodies. Fluorescence imaging was performed at Adelaide Microscopy (The University of Adelaide) and the Centre for Cancer Biology (UniSA). Electron microscopy was performed at the Ian Holmes Imaging Centre, Bio21, The University of Melbourne ( www.microscopy.unimelb.edu.au ). For provision of the SLI-TGD vector, we thank Dr. Tobias Spielmann. We thank Dr. Brad Sleebs for Compound 1. We thank the Australian Red Cross Blood Bank for the provision of human blood that was collected with informed consent of the donors. We thank the VEuPathDB team, as access to their database enabled much of this research. This work was supported by funding from the NHMRC (Project Grant APP1143974, D.W.W.), University of Adelaide Beacon Fellowship and Hospital Research Foundation Fellowship (D.W.W.), DAAD/Universities Australia joint research co-operation scheme (T.G., D.W.W., B.L., J.B.), Australian Government Research Training Program Scholarship (B.L., J.B.), South Australian Commonwealth Scholarship (B.L.), DFG BA5213/3-1 (J.S.W.) and Jürgen Manchot-Stiftung fellowship (A.A.). HAGlmS Publisher Copyright: © 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Merozoite invasion of host red blood cells (RBCs) is essential for survival of the human malaria parasite Plasmodium falciparum. Proteins involved with RBC binding and invasion are secreted from dual-club shaped organelles at the apical tip of the merozoite called the rhoptries. Here we characterise P. falciparum Cytosolically Exposed Rhoptry Leaflet Interacting protein 2 (PfCERLI2), as a rhoptry bulb protein that is essential for merozoite invasion. Phylogenetic analyses show that cerli2 arose through an ancestral gene duplication of cerli1. We show that PfCERLI2 is essential for blood-stage growth and localises to the cytosolic face of the rhoptry bulb. Inducible knockdown of PfCERLI2 led to a proportion of merozoites failing to invade and was associated with elongation of the rhoptry organelle during merozoite development and inhibition of rhoptry antigen processing. These findings identify PfCERLI2 as a protein that has key roles in rhoptry biology during merozoite invasion.
AB - Merozoite invasion of host red blood cells (RBCs) is essential for survival of the human malaria parasite Plasmodium falciparum. Proteins involved with RBC binding and invasion are secreted from dual-club shaped organelles at the apical tip of the merozoite called the rhoptries. Here we characterise P. falciparum Cytosolically Exposed Rhoptry Leaflet Interacting protein 2 (PfCERLI2), as a rhoptry bulb protein that is essential for merozoite invasion. Phylogenetic analyses show that cerli2 arose through an ancestral gene duplication of cerli1. We show that PfCERLI2 is essential for blood-stage growth and localises to the cytosolic face of the rhoptry bulb. Inducible knockdown of PfCERLI2 led to a proportion of merozoites failing to invade and was associated with elongation of the rhoptry organelle during merozoite development and inhibition of rhoptry antigen processing. These findings identify PfCERLI2 as a protein that has key roles in rhoptry biology during merozoite invasion.
UR - http://www.scopus.com/inward/record.url?scp=85124325568&partnerID=8YFLogxK
U2 - 10.1038/s42003-022-03020-9
DO - 10.1038/s42003-022-03020-9
M3 - Article
C2 - 35140336
AN - SCOPUS:85124325568
VL - 5
JO - Communications Biology
JF - Communications Biology
SN - 2399-3642
IS - 1
M1 - 121
ER -