intravital imaging; autophagy; lipases; Liver stage; parasite egress; host-pathogen interaction; Malaria; signalling; CRISPR/Cas9
Bindschedler Annina, Wacker Rahel, Egli Jessica, Eickel Nina, Schmuckli-Maurer Jacqueline, Franke-Fayard Blandine M., Janse Chris J., Heussler Volker T. (2021), Plasmodium berghei sporozoites in nonreplicative vacuole are eliminated by a PI3P ‐mediated autophagy‐independent pathway, in
Cellular Microbiology, 1-16.
Putrianti Elyzana Dewi, Schmidt-Christensen Anja, Heussler Volker, Matuschewski Kai, Ingmundson Alyssa (2020), A Plasmodium cysteine protease required for efficient transition from the liver infection stage, in
{PLOS} Pathogens, 16(9), 1008891-1008891.
de Niz Mariana, Kaiser Gesine, Zuber Benoit, Heo Won Do, Heussler Volker T, Nersesian Carolina Agop (2020), Hijacking of the host cell Golgi by Plasmodium liver stage parasites, in
bioRxiv, 1-31.
Brancucci N.M.B., Heussler V.T., Grüring C. (2020), Targeting Plasmodium Plasmepsin V: Hitting Two Birds with One Stone, in
Trends in Parasitology, 36(2), 85-87.
Lopez Maria Jose Valencia, Schimmeck Hanna, Gropengießer Julia, Middendorf Lukas, Quitmann Melanie, Schneider Carola, Holstermann Barbara, Wacker Rahel, Heussler Volker, Reimer Rudolph, Aepfelbacher Martin, Ruckdeschel Klaus (2019), Activation of the macroautophagy pathway by Yersinia enterocolitica promotes intracellular multiplication and egress of yersiniae from epithelial cells, in
Cellular Microbiology, 13046-13046.
Niklaus L., Agop-Nersesian C., Schmuckli-Maurer J., Wacker R., Gruenig V., Heussler V. T. (2019), Deciphering host lysosome-mediated elimination of Plasmodium berghei liver stage parasites, in
Scientific Reports, 9(1), 1-15.
Stanway R.R., Bushell E., Chiappino-Pepe A., Roques M., Sanderson T., Franke-Fayard B., Caldelari R., Golomingi M., Nyonda M., Pandey V., Schwach F., Chevalley S., Ramesar J., Metcalf T., Herd C., Burda P.-C., Rayner J.C., Soldati-Favre D., Janse C.J., Hatzimanikatis V., Billker O., Heussler V.T. (2019), Genome-Scale Identification of Essential Metabolic Processes for Targeting the Plasmodium Liver Stage, in
Cell, 179(5), 1112-1128.
Caldelari R., Dogga S., Schmid M.W., Franke-Fayard B., Janse C.J., Soldati-Favre D., Heussler V. (2019), Transcriptome analysis of Plasmodium berghei during exo-erythrocytic development, in
Malaria Journal, 18(1), 1-20.
Agop-Nersesian Carolina, Niklaus Livia, Wacker Rahel, Heussler Volker Theo (2018), Host cell cytosolic immune response during Plasmodium liver stage development, in
{FEMS} Microbiology Reviews, 42(3), 324-334.
De Niz M., Meibalan E., Mejia P., Ma S., Brancucci N.M.B., Agop-Nersesian C., Mandt R., Ngotho P., Hughes K.R., Waters A.P., Huttenhower C., Mitchell J.R., Martinelli R., Frischknecht F., Seydel K.B., Taylor T., Milner D., Heussler V.T., Marti M. (2018), Plasmodium gametocytes display homing and vascular transmigration in the host bone marrow, in
Science Advances, 4(5), 1-15.
Agop-Nersesian Carolina, De Niz Mariana, Niklaus Livia, Prado Monica, Eickel Nina, Heussler Volker T. (2017), Shedding of host autophagic proteins from the parasitophorous vacuolar membrane of Plasmodium berghei, in
Scientific Reports, 7(1), 2191-2191.
Saini Ekta, Zeeshan Mohammad, Brady Declan, Pandey Rajan, Kaiser Gesine, Koreny Ludek, Kumar Pradeep, Thakur Vandana, Tatiya Shreyansh, Katris Nicholas J., Limenitakis Rebecca Stanway, Kaur Inderjeet, Green Judith L., Bottrill Andrew R., Guttery David S., Waller Ross F., Heussler Volker, Holder Anthony A., Mohmmed Asif, Malhotra Pawan, Tewari Rita (2017), Photosensitized INA-Labelled protein 1 (PhIL1) is novel component of the inner membrane complex and is required for Plasmodium parasite development, in
Scientific Reports, 7(1), 15577-15577.
Kaiser Gesine, De Niz Mariana, Burda Paul-Christian, Niklaus Livia, Stanway Rebecca Limenitakis, Heussler Volker (2017), Generation of transgenic rodent malaria parasites by transfection of cell culture-derived merozoites, in
Malaria Journal, 16(1), 305-305.
Pino Paco, Caldelari Reto, Mukherjee Budhaditya, Vahokoski Juha, Klages Natacha, Maco Bohumil, Collins Christine R., Blackman Michael J., Kursula Inari, Heussler Volker, Brochet Mathieu, Soldati-Favre Dominique (2017), A multistage antimalarial targets the plasmepsins IX and X essential for invasion and egress, in
Science, 358(6362), 522-528.
Hopp Christine S., Bennett Brandy L., Mishra Satish, Lehmann Christine, Hanson Kirsten K., Lin Jing-wen, Rousseau Kimberly, Carvalho Filomena A., van der Linden Wouter A., Santos Nuno C., Bogyo Matthew, Khan Shahid M., Heussler Volker, Sinnis Photini (2017), Deletion of the rodent malaria ortholog for falcipain-1 highlights differences between hepatic and blood stage merozoites, in
PLOS Pathogens, 13(9), e1006586-e1006586.
Burda Paul-Christian, Caldelari Reto, Heussler Volker T. (2017), Manipulation of the Host Cell Membrane during Plasmodium Liver Stage Egress, in
mBio, 8(2), 1-12.
De Niz Mariana, Burda Paul-Christian, Kaiser Gesine, del Portillo Hernando A., Spielmann Tobias, Frischknecht Freddy, Heussler Volker T. (2017), Progress in imaging methods: insights gained into Plasmodium biology, in
Nature Reviews Microbiology, 15(1), 37-54.
Burda Paul-Christian, Schaffner Marco, Kaiser Gesine, Roques Magali, Zuber Beno\^ıt, Heussler Volker T. (2017), A Plasmodium plasma membrane reporter reveals membrane dynamics by live-cell microscopy, in
Scientific Reports, 7(1), 1-14.
Heussler Volker (2016), The machinery underlying malaria parasite virulence is conserved between rodent and human malaria parasites, in
Nature communications, 27225796.
Transcriptome analysis of Plasmodium berghei during exo-erythrocytic development
| Author |
Caldelari, Reto; Dogga, Sunil; Schmid, Marc W.; Franke-Fayard, Blandine; Janse, Chris J.; Soldati-Favre, Dominique; Heussler, Volker |
| Publication date |
24.12.2019 |
| Persistent Identifier (PID) |
10.1186/s12936-019-2968-7 |
| Repository |
European Nucleotide Archive
|
| Abstract |
AbstractBackgroundThe complex life cycle of malaria parasites requires well-orchestrated stage specific gene expression. In the vertebrate host the parasites grow and multiply by schizogony in two different environments: within erythrocytes and within hepatocytes. Whereas erythrocytic parasites are well-studied in this respect, relatively little is known about the exo-erythrocytic stages.Methods In an attempt to fill this gap, genome wide RNA-seq analyses of various exo-erythrocytic stages of Plasmodium berghei including sporozoites, samples from a time-course of liver stage development and detached cells were performed. These latter contain infectious merozoites and represent the final step in exo-erythrocytic development. Results The analysis represents the complete transcriptome of the entire life cycle of P. berghei parasites with temporal detailed analysis of the liver stage allowing comparison of gene expression across the progression of the life cycle. These RNA-seq data from different developmental stages were used to cluster genes with similar expression profiles, in order to infer their functions. A comparison with published data from other parasite stages confirmed stage-specific gene expression and revealed numerous genes that are expressed differentially in blood and exo-erythrocytic stages. One of the most exo-erythrocytic stage-specific genes was PBANKA_1003900, which has previously been annotated as a “gametocyte specific protein”. The promoter of this gene drove high GFP expression in exo-erythrocytic stages, confirming its expression profile seen by RNA-seq. Conclusions The comparative analysis of the genome wide mRNA expression profiles of erythrocytic and different exo-erythrocytic stages could be used to improve the understanding of gene regulation in Plasmodium parasites and can be used to model exo-erythrocytic stage metabolic networks toward the identification of differences in metabolic processes during schizogony in erythrocytes and hepatocytes.
Genome-Scale Identification of Essential Metabolic Processes for Targeting the Plasmodium Liver Stage
| Author |
Stanway, Rebecca R.; Bushell, Ellen; Chiappino-Pepe, Anush; Roques, Magali; Sanderson, Theo; Franke-Fayard, Blandine; Caldelari, Reto; Golomingi, Murielle; Nyonda, Mary; Pandey, Vikash; Schwach, Frank; Chevalley, Séverine; Ramesar, Jai; Metcalf, Tom; Herd, Colin; Burda, Paul-Christian; Rayner, Julian C.; Soldati-Favre, Dominique; Janse, Chris J.; Hatzimanikatis, Vassily; Billker, Oliver; Heussler, Volker T. |
| Publication date |
01.11.2019 |
| Persistent Identifier (PID) |
10.1016/j.cell.2019.10.030 |
| Repository |
GitHub
|
|
Genome-Scale Identification of Essential Metabolic Processes for Targeting the Plasmodium Liver Stage
| Author |
Stanway, Rebecca R.; Bushell, Ellen; Chiappino-Pepe, Anush; Roques, Magali; Sanderson, Theo; Franke-Fayard, Blandine; Caldelari, Reto; Golomingi, Murielle; Nyonda, Mary; Pandey, Vikash; Schwach, Frank; Chevalley, Séverine; Ramesar, Jai; Metcalf, Tom; Herd, Colin; Burda, Paul-Christian; Rayner, Julian C.; Soldati-Favre, Dominique; Janse, Chris J.; Hatzimanikatis, Vassily; Billker, Oliver; Heussler, Volker T. |
| Publication date |
01.11.2019 |
| Persistent Identifier (PID) |
10.1016/j.cell.2019.10.030 |
| Repository |
LCSB
|
|
During the current funding period, we could show that egress of Plasmodium parasites is initiated by the activation of a parasite-derived phospholipase (PbPL for P. berghei phospholipase) that is involved in the destruction of the parasitophorous vacuole membrane (PVM). Furthermore, we could define a new host cell autophagy pathway that is involved in the recognition and labeling of the PVM in infected hepatocytes. For the next funding period, we propose to concentrate on these two successfully initiated projects, both centered on the role of the PVM during parasite development and egress. Parasite egress from hepatocytes is clearly separated into two phases. One is the destruction of the PVM, liberating merozoites into the cytosol of the host cell. This phase is followed by the transport of merozoites, within host cell-derived vesicles (merosomes), into the blood stream where they are liberated from the host cell to infect red blood cells (RBCs). To decipher parasite egress, we will concentrate on the molecular events relating to PVM rupture. It appears that phospholipases play a crucial role in this event and we have identified putative phospholipases that localize to the PVM at the end of liver stage development. Their roles will be investigated using reverse genetics. Interaction partners of the PVM-localized phospholipases will be identified to understand how the activity of phospholipases is regulated. In addition we will continue to further analyze the activation of PbPL and in particular whether proteases play a role in this process. For the second part of this project, we propose to further investigate the role of host cell autophagy in parasite elimination as well as strategies used by the parasite to escape this host cell response and even to use it as an additional source of nutrients. In particular, we plan to manipulate autophagy pathways by genetic modification of the host cell using the powerful CRISPR/Cas9 technology.