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PhenoPlasm: a database of disruption phenotypes for malaria parasite genes

4 August 2017 - 8:08am
Wellcome Open Research, Vol. 2 (21 June 2017), 45, doi:10.12688/wellcomeopenres.11896.1
Theo Sanderson, Julian Rayner
Categories: malaria news feeds

An improved Plasmodium cynomolgi genome assembly reveals an unexpected methyltransferase gene expansion

3 August 2017 - 12:39pm
Wellcome Open Research, Vol. 2 (16 June 2017), 42, doi:10.12688/wellcomeopenres.11864.1
Erica Pasini, Ulrike Böhme, Gavin Rutledge, Annemarie Voorberg-Van der Wel, Mandy Sanders, Matt Berriman, Clemens Kocken, Thomas Otto
Categories: malaria news feeds

Rapid evolution of female-biased genes among four species of Anopheles malaria mosquitoes

3 August 2017 - 12:22pm
Genome Research (26 July 2017), gr.217216.116, doi:10.1101/gr.217216.116

An international, peer-reviewed genome sciences journal featuring outstanding original research that offers novel insights into the biology of all organisms
Francesco Papa, Nikolai Windbichler, Robert Waterhouse, Alessia Cagnetti, Rocco D'Amato, Tania Persampieri, Mara Lawniczak, Tony Nolan, Philippos Papathanos
Categories: malaria news feeds

The exported chaperone Hsp70-x supports virulence functions for Plasmodium falciparum blood stage parasites

27 July 2017 - 10:09am
PLOS ONE, Vol. 12, No. 7. (21 July 2017), e0181656, doi:10.1371/journal.pone.0181656

Malaria is caused by five different Plasmodium spp. in humans each of which modifies the host erythrocyte to survive and replicate. The two main causes of malaria, P. falciparum and P. vivax, differ in their ability to cause severe disease, mainly due to differences in the cytoadhesion of infected erythrocytes (IE) in the microvasculature. Cytoadhesion of P. falciparum in the brain leads to a large number of deaths each year and is a consequence of exported parasite proteins, some of which modify the erythrocyte cytoskeleton while others such as PfEMP1 project onto the erythrocyte surface where they bind to endothelial cells. Here we investigate the effects of knocking out an exported Hsp70-type chaperone termed Hsp70-x that is present in P. falciparum but not P. vivax. Although the growth of Δhsp70-x parasites was unaffected, the export of PfEMP1 cytoadherence proteins was delayed and Δhsp70-x IE had reduced adhesion. The Δhsp70-x IE were also more rigid than wild-type controls indicating changes in the way the parasites modified their host erythrocyte. To investigate the cause of this, transcriptional and translational changes in exported and chaperone proteins were monitored and some changes were observed. We propose that PfHsp70-x is not essential for survival in vitro, but may be required for the efficient export and functioning of some P. falciparum exported proteins.
Sarah Charnaud, Matthew Dixon, Catherine Nie, Lia Chappell, Paul Sanders, Thomas Nebl, Eric Hanssen, Matthew Berriman, Jo-Anne Chan, Adam Blanch, James Beeson, Julian Rayner, Jude Przyborski, Leann Tilley, Brendan Crabb, Paul Gilson
Categories: malaria news feeds

Functional Profiling of a Plasmodium Genome Reveals an Abundance of Essential Genes

20 July 2017 - 12:15pm
Cell, Vol. 170, No. 2. (July 2017), pp. 260-272.e8, doi:10.1016/j.cell.2017.06.030
Ellen Bushell, Ana Gomes, Theo Sanderson, Burcu Anar, Gareth Girling, Colin Herd, Tom Metcalf, Katarzyna Modrzynska, Frank Schwach, Rowena Martin, Michael Mather, Geoffrey McFadden, Leopold Parts, Gavin Rutledge, Akhil Vaidya, Kai Wengelnik, Julian Rayner, Oliver Billker
Categories: malaria news feeds

Rapid identification of genes controlling virulence and immunity in malaria parasites

20 July 2017 - 11:54am
PLOS Pathogens, Vol. 13, No. 7. (12 July 2017), e1006447, doi:10.1371/journal.ppat.1006447

Identifying the genetic determinants of phenotypes that impact disease severity is of fundamental importance for the design of new interventions against malaria. Here we present a rapid genome-wide approach capable of identifying multiple genetic drivers of medically relevant phenotypes within malaria parasites via a single experiment at single gene or allele resolution. In a proof of principle study, we found that a previously undescribed single nucleotide polymorphism in the binding domain of the erythrocyte binding like protein (EBL) conferred a dramatic change in red blood cell invasion in mutant rodent malaria parasites Plasmodium yoelii. In the same experiment, we implicated merozoite surface protein 1 (MSP1) and other polymorphic proteins, as the major targets of strain-specific immunity. Using allelic replacement, we provide functional validation of the substitution in the EBL gene controlling the growth rate in the blood stages of the parasites. Developing a greater understanding of malaria genetics is a key step in combating the threat posed by the disease. Here we use a novel approach to study two important properties of the parasite; the rate at which parasites grow within a single host, and the means by which parasites are affected by the host immune system. Two malaria strains with different biological properties were crossed in mosquitoes to produce a hybrid population, which was then grown in naïve and vaccinated mice. Parasites with genes conveying increased growth or immune evasion are favoured under natural selection, leaving a signature on the genetic composition of the cross population. We describe a novel mathematical approach to interpret this signature, identifying selected genes within the parasite population. We discover new genetic variants conveying increased within-host growth and resistance to host immunity in a mouse malaria strain. Experimental validation highlights the ability of this rapid experimental process for generating insights into malaria biology.
Hussein Abkallo, Axel Martinelli, Megumi Inoue, Abhinay Ramaprasad, Phonepadith Xangsayarath, Jesse Gitaka, Jianxia Tang, Kazuhide Yahata, Augustin Zoungrana, Hayato Mitaka, Arita Acharjee, Partha Datta, Paul Hunt, Richard Carter, Osamu Kaneko, Ville Mustonen, Christopher Illingworth, Arnab Pain, Richard Culleton
Categories: malaria news feeds

Common Piezo1 allele in African populations causes xerocytosis and attenuates Plasmodium infection

7 July 2017 - 10:00am
bioRxiv (06 July 2017), 159830, doi:10.1101/159830

bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution
Shang Ma, Stuart Cahalan, Rakhee Lohia, Gregory LaMonte, Weizheng Zeng, Swetha Murthy, Emma Paytas, Nathan Grubaugh, Ramya Gamini, Laurence Berry, Viktor Lukacs, Tess Whitwam, Meaghan Loud, Andrew Su, Kristian Andersen, Elizabeth Winzeler, Eric Honore, Kai Wengelnik, Ardem Patapoutian
Categories: malaria news feeds

Nutrient sensing modulates malaria parasite virulence

6 July 2017 - 10:50am
Nature, Vol. advance online publication (05 July 2017), doi:10.1038/nature23009
Liliana Mancio-Silva, Ksenija Slavic, Margarida Grilo Ruivo, Ana Grosso, Katarzyna Modrzynska, Iset Vera, Joana Sales-Dias, Ana Gomes, Cameron MacPherson, Pierre Crozet, Mattia Adamo, Elena Baena-Gonzalez, Rita Tewari, Manuel Llinás, Oliver Billker, Maria Mota
Categories: malaria news feeds

Nutrient sensing modulates malaria parasite virulence

6 July 2017 - 4:59am
Nature, Vol. advance online publication (05 July 2017), doi:10.1038/nature23009
Liliana Mancio-Silva, Ksenija Slavic, Margarida Grilo Ruivo, Ana Grosso, Katarzyna Modrzynska, Iset Vera, Joana Sales-Dias, Ana Gomes, Cameron MacPherson, Pierre Crozet, Mattia Adamo, Elena Baena-Gonzalez, Rita Tewari, Manuel Llinás, Oliver Billker, Maria Mota
Categories: malaria news feeds

Panoptes: web-based exploration of large scale genome variation data

30 June 2017 - 9:59am
Bioinformatics (23 June 2017), doi:10.1093/bioinformatics/btx410
Paul Vauterin, Ben Jeffery, Alistair Miles, Roberto Amato, Lee Hart, Ian Wright, Dominic Kwiatkowski
Categories: malaria news feeds

Human vaccination against Plasmodium vivax Duffy-binding protein induces strain-transcending antibodies

23 June 2017 - 10:48am
JCI Insight, Vol. 2, No. 12. (15 June 2017), doi:10.1172/jci.insight.93683
Ruth Payne, Sarah Silk, Sean Elias, Kathryn Milne, Thomas Rawlinson, David Llewellyn, Rushdi Shakri, Jing Jin, Geneviève Labbé, Nick Edwards, Ian Poulton, Rachel Roberts, Ryan Farid, Thomas Jørgensen, Daniel Alanine, Simone de Cassan, Matthew Higgins, Thomas Otto, James McCarthy, Willem de Jongh, Alfredo Nicosia, Sarah Moyle, Adrian Hill, Eleanor Berrie, Chetan Chitnis, Alison Lawrie, Simon Draper
Categories: malaria news feeds

Cracking Ali Baba?s code

22 June 2017 - 10:21am
eLife, Vol. 6 (14 June 2017), doi:10.7554/elife.28600
Oliver Billker
Categories: malaria news feeds

Targeting host factors to circumvent anti-malarial drug resistance.

19 June 2017 - 2:37pm
Current pharmaceutical design, Vol. 19, No. 2. (2013), pp. 290-299

The most common treatments for infectious diseases target the invading pathogen. The efficacy of such an approach may, however, be countered by the possibility of the development of resistance to a pharmacophore, through mutation(s) in pathogen molecules required for activity. Given the fact that pathogens exploit host factors in order to grow in an otherwise hostile environment, one possible way to circumvent the emergence of resistance is to develop drugs that target non-essential host factors hijacked by the pathogen, rather than the pathogen's own molecules. Such solutions are already being developed for various viral and bacterial pathogens, but much less has been achieved with infections caused by protozoan parasites, as is the case of Plasmodium. Here, we highlight recent progress in host target-based anti-viral and anti-bacterial approaches and discuss possible host targets that may be used for anti-malarial interventions. Host molecules that play a role during either the liver or the blood stage of Plasmodium infection are outlined and their potential merits as anti-malarial targets are discussed.
Miguel Prudêncio, Maria Mota
Categories: malaria news feeds

Proteomic profiling of the brain of mice with experimental cerebral malaria

14 June 2017 - 11:49am
Journal of Proteomics (June 2017), doi:10.1016/j.jprot.2017.06.002

Cerebral malaria (CM) is a severe neurological complication of malaria infection in both adults and children. In pursuit of effective treatment of CM, clinical studies, postmortem analysis and animal models have been employed to understand the pathology and identify effective interventions. In this study, a shotgun proteomics analysis was conducted to profile the proteomic signature of the brain tissue of mice with experimental cerebral malaria (ECM) in order to further understand the underlying pathology. To identify CM-associated response, proteomic signatures of the brains of C57/Bl6N mice infected with P. berghei ANKA that developed neurological syndrome were compared to those of mice infected with P. berghei NK65 that developed equally high parasite burdens without neurological signs, and to those of non-infected mice. The results show that the CM-associated response in mice that developed neurological signs comprise mainly acute-phase reaction and coagulation cascade activation, and indicate the leakage of plasma proteins into the brain parenchyma. Cerebral malaria (CM) remains a major cause of death in children. The majority of these deaths occur in sub-Saharan Africa. Even with adequate access to treatment, mortality remains high and neurological sequelae can be found in up to 20% of survivors. No adjuvant treatment to date has been shown to reduce mortality and the pathophysiology of CM is largely unknown. Experimental cerebral malaria (ECM) is a well-established model that may contribute to identify and test druggable targets. In this study we have identified the disruption of the blood-brain barrier following inflammatory and vascular injury as a mechanism of disease. In this study we report a number of proteins that could be validated as potential biomarkers of ECM. Further studies, will be required to validate the clinical relevance of these biomarkers in human CM.
Ehab Moussa, Honglei Huang, Malika Ahras, Amar Lall, Marie Thezenas, Roman Fischer, Benedikt Kessler, Arnab Pain, Oliver Billker, Climent Casals-Pascual
Categories: malaria news feeds

Human Migration And The Spread Of Malaria Parasites To The New World

8 June 2017 - 12:33pm
bioRxiv (29 May 2017), 141853, doi:10.1101/141853

bioRxiv - the preprint server for biology, operated by Cold Spring Harbor Laboratory, a research and educational institution
Priscila Rodrigues, Hugo Valdivia, Thais Oliveira, Joao Marcelo, Ana Maria, Crispim Cerutti-Junior, Julyana Buery, Cristiana Brito, Julio Souza, Zelinda Maria Braga Hirano, Rosely Malafronte, Simone Ladeia-Andrade, Toshihiro Mita, Ana Santamaria, Jose Calzada, Fumihiko Kawamoto, Leonie Raijmakers, Ivo Mueller, Maria Pacheco, Ananias Escalante, Ingrid Felger, Marcelo Ferreira
Categories: malaria news feeds

Malaria host candidate genes validated by association with current, recent and historic measures of transmission intensity.

1 June 2017 - 10:47am
The Journal of infectious diseases (25 May 2017)

Human malaria susceptibility is determined by multiple genetic factors. It is however unclear which genetic variants remain important over time. Genetic associations of 175 high quality polymorphisms within several malaria candidate genes were examined in a sample of 8,096 individuals from northeast Tanzania using altitude, seroconversion rates and parasite rates as proxies of historical, recent and current malaria transmission intensity. A principal component (PC) analysis was used to derive two alternative measures of overall malaria propensity of a location across different time scales. Common red blood cell polymorphisms (i.e., HbS, G6PD and α-thalassaemia) were the only ones to be associated with all three measures of transmission intensity and the first PC. Moderate associations were found between some immune response genes (i.e., IL3 and IL13) and parasite rates, but these could not be reproduced using the alternative measures of malaria propensity. We have demonstrated the potential of using altitude and seroconversion rate as measures of malaria transmission capturing medium to long term time scales to detect genetic associations that are likely to persist over time. These measures also have the advantage of minimizing the deleterious effects of random factors affecting parasite rates on the respective association signals.
Nuno Sepúlveda, Alphaxard Manjurano, Susana Campino, Martha Lemnge, John Lusingu, Raimos Olomi, Kirk Rockett, Christina Hubbart, Anna Jeffreys, Kate Rowlands, , Taane Clark, Eleanor Riley, Chris Drakeley
Categories: malaria news feeds

GWAS of self-reported mosquito bite size, itch intensity and attractiveness to mosquitoes implicates immune-related predisposition loci

25 May 2017 - 9:08am
Human Molecular Genetics, Vol. 26, No. 7. (01 April 2017), pp. 1391-1406, doi:10.1093/hmg/ddx036
Amy Jones, Mera Tilley, Alex Gutteridge, Craig Hyde, Michael Nagle, Daniel Ziemek, Donal Gorman, Eric Fauman, Xing Chen, Melissa Miller, Chao Tian, Youna Hu, David Hinds, Peter Cox, Serena Scollen
Categories: malaria news feeds

Resistance to malaria through structural variation of red blood cell invasion receptors

19 May 2017 - 6:28pm
Science (18 May 2017), eaam6393, doi:10.1126/science.aam6393
Ellen Leffler, Gavin Band, George Busby, Katja Kivinen, Quang Le, Geraldine Clarke, Kalifa Bojang, David Conway, Muminatou Jallow, Fatoumatta Sisay-Joof, Edith Bougouma, Valentina Mangano, David Modiano, Sodiomon Sirima, Eric Achidi, Tobias Apinjoh, Kevin Marsh, Carolyne Ndila, Norbert Peshu, Thomas Williams, Chris Drakeley, Alphaxard Manjurano, Hugh Reyburn, Eleanor Riley, David Kachala, Malcolm Molyneux, Vysaul Nyirongo, Terrie Taylor, Nicole Thornton, Louise Tilley, Shane Grimsley, Eleanor Drury, Jim Stalker, Victoria Cornelius, Christina Hubbart, Anna Jeffreys, Kate Rowlands, Kirk Rockett, Chris Spencer, Dominic Kwiatkowski, Malaria Genomic Epidemiology Network
Categories: malaria news feeds

Geographic-genetic analysis of Plasmodium falciparum parasite populations from surveys of primary school children in Western Kenya

18 May 2017 - 12:36pm
Wellcome Open Research, Vol. 2 (20 April 2017), 29, doi:10.12688/wellcomeopenres.11228.1
Irene Omedo, Polycarp Mogeni, Kirk Rockett, Alice Kamau, Christina Hubbart, Anna Jeffreys, Lynette Ochola-Oyier, Etienne de Villiers, Caroline Gitonga, Abdisalan Noor, Robert Snow, Dominic Kwiatkowski, Philip Bejon
Categories: malaria news feeds

Artemisinin resistance without pfkelch13 mutations in Plasmodium falciparum isolates from Cambodia

18 May 2017 - 12:30pm
Malaria Journal, Vol. 16, No. 1. (12 May 2017), doi:10.1186/s12936-017-1845-5
Angana Mukherjee, Selina Bopp, Pamela Magistrado, Wesley Wong, Rachel Daniels, Allison Demas, Stephen Schaffner, Chanaki Amaratunga, Pharath Lim, Mehul Dhorda, Olivo Miotto, Charles Woodrow, Elizabeth Ashley, Arjen Dondorp, Nicholas White, Dyann Wirth, Rick Fairhurst, Sarah Volkman
Categories: malaria news feeds