Interaction of Malaria Parasites With the Host Disease Pathogenesis and Control

PTRAMP, CSS and Ripr form a conserved complex required for merozoite invasion of Plasmodium species into erythrocytes

BA Seager, PS Lim, X Xiao, KH Lai, LB Feufack-Donfack, S Dass, NC Jung, A Abraham, MJ Grigg, NM Anstey, T William, J Sattabongkot, A Leis, RJ Longley, MT Duraisingh, J Popovici, DW Wilson, AF Cowman, SW Scally

2026-12-01

Invasion of erythrocytes by members of the Plasmodium genus is an essential step of the parasite lifecycle, orchestrated by numero..

PCRCR complex is essential for invasion of human erythrocytes by Plasmodium falciparum

SW Scally, T Triglia, C Evelyn, BA Seager, M Pasternak, PS Lim, J Healer, ND Geoghegan, A Adair, WH Tham, LF Dagley, KL Rogers, AF Cowman

2022-12-01

The most severe form of malaria is caused by Plasmodium falciparum. These parasites invade human erythrocytes, and an essential st..

RhopH2 and RhopH3 export enables assembly of the RhopH complex on P. falciparum-infected erythrocyte membranes

M Pasternak, JMJ Verhoef, W Wong, T Triglia, MJ Mlodzianoski, N Geoghegan, C Evelyn, AZ Wardak, K Rogers, AF Cowman

2022-12-01

RhopH complexes consists of Clag3, RhopH2 and RhopH3 and are essential for growth of Plasmodium falciparum inside infected erythro..

Comparison of Antibody Responses and Parasite Clearance in Artemisinin Therapeutic Efficacy Studies in the Democratic Republic of Congo and Asia

JC Cutts, K O’Flaherty, SG Zaloumis, EA Ashley, JA Chan, MA Onyamboko, C Fanello, AM Dondorp, NP Day, AP Phyo, M Dhorda, M Imwong, RM Fairhurst, P Lim, C Amaratunga, S Pukrittayakamee, TT Hien, Y Htut, M Mayxay, M Abdul Faiz

2022-07-15

Background. Understanding the effect of immunity on Plasmodium falciparum clearance is essential for interpreting therapeutic effi..

Development and application of a high-throughput screening assay for identification of small molecule inhibitors of the P. falciparum reticulocyte binding-like homologue 5 protein

BE Sleebs, KE Jarman, S Frolich, W Wong, J Healer, W Dai, IS Lucet, DW Wilson, AF Cowman

2020-12-01

The P. falciparum parasite, responsible for the disease in humans known as malaria, must invade erythrocytes to provide an environ..

A 4-cyano-3-methylisoquinoline inhibitor of Plasmodium falciparum growth targets the sodium efflux pump PfATP4

PR Gilson, R Kumarasingha, J Thompson, X Zhang, JS Penington, R Kalhor, HE Bullen, AM Lehane, MG Dans, TF de Koning-Ward, JK Holien, TP Soares da Costa, MD Hulett, MJ Buskes, BS Crabb, K Kirk, AT Papenfuss, AF Cowman, BM Abbott

2019-12-01

We developed a novel series of antimalarial compounds based on a 4-cyano-3-methylisoquinoline. Our lead compound MB14 achieved mod..

Spatial organization of protein export in malaria parasite blood stages

SC Charnaud, TK Jonsdottir, PR Sanders, HE Bullen, BK Dickerman, B Kouskousis, CS Palmer, HM Pietrzak, AE Laumaea, AB Erazo, E McHugh, L Tilley, BS Crabb, PR Gilson

2018-08-01

Plasmodium falciparum, which causes malaria, extensively remodels its human host cells, particularly erythrocytes. Remodelling is ..

A genetic screen in rodent malaria parasites identifies five new apicoplast putative membrane transporters, one of which is essential in human malaria parasites

CP Sayers, V Mollard, HD Buchanan, GI McFadden, CD Goodman

2018-01-01

The malaria-causing parasite, Plasmodium, contains a unique non-photosynthetic plastid known as the apicoplast. The apicoplast is ..

The Molecular Basis of Erythrocyte Invasion by Malaria Parasites

AF Cowman, CJ Tonkin, WH Tham, MT Duraisingh

2017-08-09

Plasmodium species cause malaria by proliferating in human erythrocytes. Invasion of immunologically privileged erythrocytes provi..

Plasmodium falciparum ligand binding to erythrocytes induce alterations in deformability essential for invasion

Xavier Sisquella, Thomas Nebr, Jennifer K Thompson, Lachlan Whitehead, Brian M Malpede, Nichole D Salinas, Kelly Rogers, Niraj H Tolia, Andrea Fleig, Joseph O'Neill, Wai-Hong Timm, F David Horgen, Alan F Cowman

2017-02-22

The most lethal form of malaria in humans is caused by Plasmodium falciparum. These parasites invade erythrocytes, a complex proce..

Structural basis for inhibition of erythrocyte invasion by antibodies to plasmodium falciparum protein CyRPA

L Chen, Y Xu, W Wong, JK Thompson, J Healer, ED Goddard-Borger, MC Lawrence, AF Cowman

2017-02-14

Plasmodium falciparum causes malaria in humans with over 450,000 deaths annually. The asexual blood stage involves invasion of ery..

Host cell remodelling in malaria parasites: a new pool of potential drug targets

PR Gilson, SA Chisholm, BS Crabb, TF de Koning-Ward

2017-02-01

When in their human hosts, malaria parasites spend most of their time housed within vacuoles inside erythrocytes and hepatocytes. ..

Proteomic analysis reveals novel proteins associated with the Plasmodium protein exporter PTEX and a loss of complex stability upon truncation of the core PTEX component, PTEX150

B Elsworth, PR Sanders, T Nebl, S Batinovic, M Kalanon, CQ Nie, SC Charnaud, HE Bullen, TF de Koning Ward, L Tilley, BS Crabb, PR Gilson

2016-11-01

The Plasmodium translocon for exported proteins (PTEX) has been established as the machinery responsible for the translocation of ..

Structure–Activity Studies of β-Hairpin Peptide Inhibitors of the Plasmodium falciparum AMA1–RON2 Interaction

G Wang, N Drinkwater, DR Drew, CA MacRaild, DK Chalmers, B Mohanty, SS Lim, RF Anders, JG Beeson, PE Thompson, S McGowan, JS Simpson, RS Norton, MJ Scanlon

2016-10-09

The interaction between apical membrane antigen 1 (AMA1) and rhoptry neck protein 2 (RON2) plays a key role in the invasion of red..

Essential Role of the PfRh5/PfRipr/CyRPA Complex during Plasmodium falciparum Invasion of Erythrocytes

JC Volz, A Yap, X Sisquella, JK Thompson, NTY Lim, LW Whitehead, L Chen, M Lampe, WH Tham, D Wilson, T Nebl, D Marapana, T Triglia, W Wong, KL Rogers, AF Cowman

2016-07-13

Plasmodium falciparum parasites in the merozoite stage invade human erythrocytes and cause malaria. Invasion requires multiple int..

Targeting of a transporter to the outer apicoplast membrane in the human malaria parasite Plasmodium falciparum

L Lim, CP Sayers, CD Goodman, GI McFadden

2016-07-01

Apicoplasts are vestigial plastids in apicomplexan parasites like Plasmodium, the causative agent of malaria. Apicomplexan parasit..

Multiple plasmodium falciparum merozoite surface protein 1 complexes mediate merozoite binding to human erythrocytes

CS Lin, AD Uboldi, C Epp, H Bujard, T Tsuboi, PE Czabotar, XAF Cowman

2016-04-01

Successful invasion of human erythrocytes by Plasmodium falciparum merozoites is required for infection of the host and parasite s..

Export of malaria proteins requires co-translational processing of the PEXEL motif independent of phosphatidylinositol-3-phosphate binding

JA Boddey, MT O'Neill, S Lopaticki, TG Carvalho, AN Hodder, T Nebl, S Wawra, P Van West, Z Ebrahimzadeh, D Richard, S Flemming, T Spielmann, J Przyborski, JJ Babon, AF Cowman

2016-02-01

Plasmodium falciparum exports proteins into erythrocytes using the Plasmodium export element (PEXEL) motif, which is cleaved in th..

Recruitment of factor H as a novel complement evasion strategy for blood-stage plasmodium falciparum infection

AT Kennedy, CQ Schmidt, JK Thompson, GE Weiss, T Taechalertpaisarn, PR Gilson, PN Barlow, BS Crabb, AF Cowman, WH Tham

2016-02-01

The human complement system is the frontline defense mechanism against invading pathogens. The coexistence of humans and microbes ..

A Toll-like receptor-1 variant and its characteristic cellular phenotype is associated with severe malaria in Papua New Guinean children

L Manning, J Cutts, DI Stanisic, M Laman, A Carmagnac, S Allen, A O'Donnell, H Karunajeewa, A Rosanas-Urgell, P Siba, TME Davis, P Michon, L Schofield, K Rockett, D Kwiatkowski, I Mueller

2016-01-01

Genetic factors are likely to contribute to low severe malaria case fatality rates in Melanesian populations, but association stud..

Infectivity of plasmodium falciparum in malaria-naive individuals is related to knob expression and cytoadherence of the parasite

DI Stanisic, J Gerrard, J Fink, PM Griffin, XQ Liu, L Sundac, S Sekuloski, IB Rodriguez, J Pingnet, Y Yang, Y Zhou, KR Trenholme, CYT Wang, H Hackett, JAA Chan, C Langer, E Hanssen, SL Hoffman, JG Beeson, JS McCarthy

2016-01-01

Plasmodium falciparum is the most virulent human malaria parasite because of its ability to cytoadhere in the microvasculature. No..

Localisation-based imaging of malarial antigens during erythrocyte entry reaffirms a role for AMA1 but not MTRAP in invasion

DT Riglar, L Whitehead, AF Cowman, KL Rogers, J Baum

2016-01-01

Microscopy-based localisation of proteins during malaria parasite (Plasmodium) invasion of the erythrocyte is widely used for tent..

Merozoite antigens of plasmodium falciparum elicit strain-transcending opsonizing immunity

DL Hill, DW Wilson, NG Sampaio, EM Eriksson, V Ryg-Cornejo, GL Abby Harrison, AD Uboldi, LJ Robinson, JG Beeson, P Siba, AF Cowman, DS Hansen, I Mueller, L Schofielda

2016-01-01

It is unclear whether naturally acquired immunity to Plasmodium falciparum results from the acquisition of antibodies to multiple,..

Differences in affinity of monoclonal and naturally acquired polyclonal antibodies against Plasmodium falciparum merozoite antigens

2015-12-12

Background: Malaria is a major global cause of deaths and a vaccine is urgently needed. Results: We have employed the P. falciparu..

Macrolides rapidly inhibit red blood cell invasion by the human malaria parasite, Plasmodium falciparum

DW Wilson, CD Goodman, BE Sleebs, GE Weiss, NWM de Jong, F Angrisano, C Langer, J Baum, BS Crabb, PR Gilson, GI McFadden, JG Beeson

2015-12-12

© 2015 Wilson et al. Background: Malaria invasion of red blood cells involves multiple parasite-specific targets that are easily a..

Mitochondrial ATP synthase is dispensable in blood-stage Plasmodium berghei rodent malaria but essential in the mosquito phase

A Sturm, V Mollard, A Cozijnsen, CD Goodman, GI McFadden

2015-08-18

Mitochondrial ATP synthase is driven by chemiosmotic oxidation of pyruvate derived from glycolysis. Blood-stage malaria parasites ..

Structural basis for plasmepsin v inhibition that blocks export of malaria proteins to human erythrocytes

AN Hodder, BE Sleebs, PE Czabotar, M Gazdik, Y Xu, MT O'Neill, S Lopaticki, T Nebl, T Triglia, BJ Smith, K Lowes, JA Boddey, AF Cowman

2015-08-07

Plasmepsin V, an essential aspartyl protease of malaria parasites, has a key role in the export of effector proteins to parasite-i..

Plasmodium falciparum Adhesins Play an Essential Role in Signalling and Activation of Invasion into Human Erythrocytes

WH Tham, NTY Lim, GE Weiss, S Lopaticki, BRE Ansell, M Bird, I Lucet, D Dorin-Semblat, C Doerig, PR Gilson, BS Crabb, AF Cowman

2015-01-01

The most severe form of malaria in humans is caused by the protozoan parasite Plasmodium falciparum. The invasive form of malaria ..

Plasmodium falciparum transfected with ultra bright nanoluc luciferase offers high sensitivity detection for the screening of growth and cellular trafficking inhibitors

MF Azevedo, CQ Nie, B Elsworth, SC Charnaud, PR Sanders, BS Crabb, PR Gilson

2014-11-13

Drug discovery is a key part of malaria control and eradication strategies, and could benefit from sensitive and affordable assays..

Crystal structure of PfRh5, an essential P. falciparum ligand for invasion of human erythrocytes

L Chen, Y Xu, J Healer, JK Thompson, BJ Smith, MC Lawrence, AF Cowman

2014-10-08

Plasmodium falciparum causes the most severe form of malaria in humans and is responsible for over 700,000 deaths annually. It is ..

A critical evaluation of pyrrolo[2,3-d]pyrimidine-4-amines as Plasmodium falciparum apical membrane antigen 1 (AMA1) inhibitors

SM Devine, SS Lim, IR Chandrashekaran, CA Macraild, DR Drew, CO Debono, R Lam, RF Anders, JG Beeson, MJ Scanlon, PJ Scammells, RS Norton

2014-10-01

We have determined that a previously reported class of pyrrolo[2,3-d]pyrimidine-4-amines exhibit low binding to apical membrane an..

The merozoite surface protein 1 complex is a platform for binding to human erythrocytes by plasmodium falciparum

CS Lin, AD Uboldi, D Marapana, PE Czabotar, C Epp, H Bujard, NL Taylor, MA Perugini, AN Hodder, AF Cowman

2014-09-12

Plasmodium falciparum is the causative agent of the most severe form of malaria in humans. The merozoite, an extracellular stage o..

Export of virulence proteins by malaria-infected erythrocytes involves remodeling of host actin cytoskeleton

M Rug, M Cyrklaff, A Mikkonen, L Lemgruber, S Kuelzer, CP Sanchez, J Thompson, E Hanssen, M O'Neill, C Langer, M Lanzer, F Frischknecht, AG Maier, AF Cowman

2014-08-19

Following invasion of human red blood cells (RBCs) by the malaria parasite, Plasmodium falciparum, a remarkable process of remodel..

γδ T cells and CD14 monocytes are predominant cellular sources of cytokines and chemokines associated with severe malaria

DI Stanisic, J Cutts, E Eriksson, FJI Fowkes, A Rosanas-Urgell, P Siba, M Laman, TME Davis, L Manning, I Mueller, L Schofield

2014-07-15

Background. Severe malaria (SM) is associated with high levels of cytokines such as tumor necrosis factor (TNF), interleukin 1 (IL..

Opsonic phagocytosis of Plasmodium falciparum merozoites: Mechanism in human immunity and a correlate of protection against malaria

FHA Osier, G Feng, MJ Boyle, C Langer, J Zhou, JS Richards, FJ McCallum, L Reiling, A Jaworowski, RF Anders, K Marsh, JG Beeson

2014-07-01

Background: An understanding of the mechanisms mediating protective immunity against malaria in humans is currently lacking, but c..

A dual-targeted aminoacyl-tRNA synthetase in Plasmodium falciparum charges cytosolic and apicoplast tRNACys

JS Pham, R Sakaguchi, LM Yeoh, NS De Silva, GI Mcfadden, YM Hou, SA Ralph

2014-03-15

Plasmodium parasites possess two endosymbiotic organelles: a mitochondrion and a relict plastid called the apicoplast. To accommod..

Conditional expression of apical membrane antigen 1 in Plasmodium falciparum shows it is required for erythrocyte invasion by merozoites

A Yap, MF Azevedo, PR Gilson, GE Weiss, MT O'Neill, DW Wilson, BS Crabb, AF Cowman

2014-01-01

Malaria is caused by obligate intracellular parasites, of which Plasmodium falciparum is the most lethal species. In humans, P.fal..

High yield purification of Plasmodium falciparum merozoites for use in opsonizing antibody assays

DL Hill, EM Eriksson, L Schofield

2014-01-01

Plasmodium falciparum merozoite antigens are under development as potential malaria vaccines. One aspect of immunity against malar..

Lysine acetylation in sexual stage malaria parasites is a target for antimalarial small molecules

K Trenholme, L Marek, S Duffy, G Pradel, G Fisher, FK Hansen, TS Skinner-Adams, A Butterworth, CJ Ngwa, J Moecking, CD Goodman, GI McFadden, SDM Sumanadasa, DP Fairlie, VM Avery, T Kurz, KT Andrews

2014-01-01

Therapies to prevent transmission of malaria parasites to the mosquito vector are a vital part of the global malaria elimination a..

PTEX is an essential nexus for protein export in malaria parasites

B Elsworth, K Matthews, CQ Nie, M Kalanon, SC Charnaud, PR Sanders, SA Chisholm, NA Counihan, PJ Shaw, P Pino, JA Chan, MF Azevedo, SJ Rogerson, JG Beeson, BS Crabb, PR Gilson, TF De Koning-Ward

2014-01-01

During the blood stages of malaria, several hundred parasite-encoded proteins are exported beyond the double-membrane barrier that..

Vaccination with Conserved Regions of Erythrocyte-Binding Antigens Induces Neutralizing Antibodies against Multiple Strains of Plasmodium falciparum

J Healer, JK Thompson, DT Riglar, DW Wilson, YHC Chiu, K Miura, L Chen, AN Hodder, CA Long, DS Hansen, J Baum, AF Cowman

2013-09-10

Background:A highly effective vaccine against Plasmodium falciparum malaria should induce potent, strain transcending immunity tha..

Opsonising Antibodies to P. falciparum Merozoites Associated with Immunity to Clinical Malaria

DL Hill, EM Eriksson, CSN Li Wai Suen, CY Chiu, V Ryg-Cornejo, LJ Robinson, PM Siba, I Mueller, DS Hansen, L Schofield

2013-09-09

Naturally acquired humoral immunity to the malarial parasite Plasmodium falciparum can protect against disease, although the preci..

Inhibition of Plasmodium falciparum CDPK1 by conditional expression of its J-domain demonstrates a key role in schizont development

MF Azevedo, PR Sanders, E Krejany, CQ Nie, P Fu, LA Bach, G Wunderlich, BS Crabb, PR Gilson

2013-06-15

PfCDPK1 [Plasmodium falciparum CDPK1 (calcium-dependent protein kinase 1)] is highly expressed in parasite asexual blood and mosqu..

Biochemical and functional analysis of two plasmodium falciparum blood-stage 6-Cys proteins: P12 and P41

T Taechalertpaisarn, C Crosnier, SJ Bartholdson, AN Hodder, J Thompson, LY Bustamante, DW Wilson, PR Sanders, GJ Wright, JC Rayner, AF Cowman, PR Gilson, BS Crabb

2012-07-27

The genomes of Plasmodium parasites that cause malaria in humans, other primates, birds, and rodents all encode multiple 6-cys pro..

Antimalarial activity of the anticancer histone deacetylase inhibitor SB939

SDM Sumanadasa, CD Goodman, AJ Lucke, T Skinner-Adams, I Saham, A Haque, TA Do, GI McFadden, DP Fairlie, KT Andrews

2012-07-01

Histone deacetylase (HDAC) enzymes posttranslationally modify lysines on histone and nonhistone proteins and play crucial roles in..

Characterization of two malaria parasite organelle translation elongation factor G proteins: The likely targets of the anti-malarial fusidic acid

RA Johnson, GI McFadden, CD Goodman

2011-06-16

Malaria parasites harbour two organelles with bacteria-like metabolic processes that are the targets of many anti-bacterial drugs...