Malaria: A Collection of Articles

Malaria remains a considerable public health burden in many parts of the world. It is caused by Plasmodium parasites, which are transmitted by mosquitoes and undergo complex developmental cycles in both the insect vector and vertebrate hosts. Malaria research has greatly benefited from technological advances in genetic engineering, next-generation sequencing and structural biology, providing new insights into parasite development and transmission, and host-parasite interactions.

This collection highlights an assembly of important papers representative of multidisciplinary malaria research, delving into fundamental questions concerning the biology of the parasite at cellular, molecular and structural levels, malaria transmission and pathogenesis, drug resistance and vaccine development.

Other relevant articles can be found on eLife's Tropical Disease: A Collection of Articles and on our subject page for Microbiology and Infectious Disease.

Collection

1. 1. Cell Biology

   Single-cell RNA-seq reveals hidden transcriptional variation in malaria parasites

   Adam J Reid, Arthur M Talman ... Mara KN Lawniczak

   Plasmodium parasite transcription shifts dramatically along asexual development, and transmission stages variably express important immune evasion genes, suggesting much interesting biology has until now been hidden by bulk analyses.
2. 1. Microbiology and Infectious Disease
   2. Structural Biology and Molecular Biophysics

   Malaria parasites use a soluble RhopH complex for erythrocyte invasion and an integral form for nutrient uptake

   Marc A Schureck, Joseph E Darling ... Sanjay A Desai

   A high-resolution structure reveals how the RhopH complex traffics within Plasmodium-infected human erythrocytes to serve divergent, essential functions.
3. 1. Cell Biology
   2. Microbiology and Infectious Disease

   Formin-2 drives polymerisation of actin filaments enabling segregation of apicoplasts and cytokinesis in Plasmodium falciparum

   Johannes Felix Stortz, Mario Del Rosario ... Sujaan Das

   Formin-2 controls spatiotemporal polymerisation of actin filaments, a common mechanism used by apicomplexans for effective segregation of essential chloroplast-like organelles called apicoplasts, and additionally for daughter formation in Plasmodium falciparum.
4. 1. Cell Biology
   2. Microbiology and Infectious Disease

   Identification of cryptic subunits from an apicomplexan ATP synthase

   Diego Huet, Esther Rajendran ... Sebastian Lourido

   A phylum-specific ATP synthase subunit is needed for proper mitochondrial function and stability of the complex in Toxoplasma gondii.
5. 1. Cell Biology
   2. Microbiology and Infectious Disease

   Multiple short windows of calcium-dependent protein kinase 4 activity coordinate distinct cell cycle events during Plasmodium gametogenesis

   Hanwei Fang, Natacha Klages ... Mathieu Brochet

   CDPK4 is a pleiotropic regulator controlling initiation of DNA replication, mitotic spindle assembly and flagellar activation during the early stages of Plasmodium transmission.
6. 1. Epidemiology and Global Health

   Modelling the contribution of the hypnozoite reservoir to Plasmodium vivax transmission

   Michael T White, Stephan Karl ... Azra C Ghani

   Mathematical models of the build-up and depletion of the hypnozoite reservoir in the liver can inform the design of treatment strategies for preventing Plasmodium vivax relapse infections.
7. 1. Microbiology and Infectious Disease

   The Plasmodium liver-specific protein 2 (LISP2) is an early marker of liver stage development

   Devendra Kumar Gupta, Laurent Dembele ... Thierry Tidiane Diagana

   LISP2 expression marks the beginning of awakening of dormant hypnozoite to developing malaria liver stages, which are susceptible to a novel prophylactic drug, Plasmodium PI4K inhibitor.
8. 1. Genetics and Genomics
   2. Microbiology and Infectious Disease

   Rapid and iterative genome editing in the malaria parasite Plasmodium knowlesi provides new tools for P. vivax research

   Franziska Mohring, Melissa Natalie Hart ... Robert William Moon

   Optimised genome editing in P. knowlesi enables transgenic expression of a lead P. vivax vaccine candidate, revealing roles in host cell tropisms and providing tools for scalable vaccine efficacy testing.
9. 1. Ecology
   2. Epidemiology and Global Health

   Tracking zoonotic pathogens using blood-sucking flies as 'flying syringes'

   Paul-Yannick Bitome-Essono, Benjamin Ollomo ... Christophe Paupy

   A field study coupled with a molecular analysis demonstrates that using hematophagous flies as 'flying syringes' could be used to investigate blood-borne pathogen diversity in wild vertebrates and act as an early detection tool of zoonotic pathogens.
10. 1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    Mapping immune variation and var gene switching in naive hosts infected with Plasmodium falciparum

    Kathryn Milne, Alasdair Ivens ... Philip J Spence

    Parasite variants associated with severe malaria do not have an intrinsic growth or survival advantage in vivo, which indicates that a change in host environment is required for their selection.
11. 1. Chromosomes and Gene Expression
    2. Microbiology and Infectious Disease

    Common virulence gene expression in adult first-time infected malaria patients and severe cases

    J Stephan Wichers, Gerry Tonkin-Hill ... Anna Bachmann

    Parasites with pathogenic variant surface antigens are common in adult malaria patients with a naive immune status.
12. 1. Epidemiology and Global Health
    2. Genetics and Genomics

    Improving statistical power in severe malaria genetic association studies by augmenting phenotypic precision

    James A Watson, Carolyne M Ndila ... Nicholas J White

    Complete blood count data can increase the accuracy of the diagnosis of severe malaria in children in high transmission settings.
13. 1. Cell Biology
    2. Microbiology and Infectious Disease

    Artemisinin exposure at the ring or trophozoite stage impacts Plasmodium falciparum sexual conversion differently

    Harvie P Portugaliza, Shinya Miyazaki ... Alfred Cortés

    Treatment of malaria parasites with the frontline antimalarial drug artemisinin can increase the proportion of parasites that convert into transmission forms.
14. 1. Genetics and Genomics
    2. Evolutionary Biology

    Current CRISPR gene drive systems are likely to be highly invasive in wild populations

    Charleston Noble, Ben Adlam ... Martin A Nowak

    If released in the wild, current CRISPR-based gene drive systems designed to alter populations could spread much farther than intended, despite the evolution of drive resistance.
15. 1. Genetics and Genomics

    Converting endogenous genes of the malaria mosquito into simple non-autonomous gene drives for population replacement

    Astrid Hoermann, Sofia Tapanelli ... Nikolai Windbichler

    Minimal genetic modifications of endogenous mosquito genes allow the tissue-specific expression of anti-malarial effectors and convert them into efficient non-autonomous gene drives.
16. 1. Immunology and Inflammation

    The structure of a LAIR1-containing human antibody reveals a novel mechanism of antigen recognition

    Fu-Lien Hsieh, Matthew K Higgins

    The structure of a human antibody in which the variable loops position a human protein LAIR1 for antigen recognition, reveals a novel and indirect mode of antibody function.
17. 1. Structural Biology and Molecular Biophysics

    Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine

    Wilson Wong, Xiao-chen Bai ... Sjors HW Scheres

    The molecular mechanism behind how emetine inhibits the ribosome of the human malaria parasite, along with structural details of the complex formed, is revealed at high resolution using cryo-electron microscopy.
18. 1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease

    Small molecule inhibition of apicomplexan FtsH1 disrupts plastid biogenesis in human pathogens

    Katherine Amberg-Johnson, Sanjay B Hari ... Ellen Yeh

    An unbiased chemical screen identifies the AAA+ membrane metalloprotease FtsH1 as a novel apicoplast biogenesis factor and druggable antimalarial target.
19. 1. Cell Biology
    2. Microbiology and Infectious Disease

    A single point mutation in the Plasmodium falciparum FtsH1 metalloprotease confers actinonin resistance

    Christopher D Goodman, Taher Uddin ... Geoffrey I McFadden

    Actinonin kills malaria parasites by targeting the apicoplast-associated metalloprotease FTSH1.
20. 1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    Plasmodium falciparum K13 mutations in Africa and Asia impact artemisinin resistance and parasite fitness

    Barbara H Stokes, Satish K Dhingra ... David A Fidock

    Plasmodium falciparum K13 mutations confer resistance to the antimalarial artemisinin in Asian and African parasites, with most gene-edited mutant K13 African parasite lines showing a fitness cost that may predict slow dissemination of artemisinin resistance in high-transmission settings.
21. 1. Biochemistry and Chemical Biology
    2. Plant Biology

    A new synthetic biology approach allows transfer of an entire metabolic pathway from a medicinal plant to a biomass crop

    Paulina Fuentes, Fei Zhou ... Ralph Bock

    A combination of chloroplast transformation with nuclear transformation and large-scale metabolic screening of supertransformed plant lines has enabled an entire biochemical pathway to be transferred from a medicinal plant to a high-biomass crop.
22. 1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    Genetic surveillance in the Greater Mekong subregion and South Asia to support malaria control and elimination

    Christopher G Jacob, Nguyen Thuy-Nhien ... Olivo Miotto

    Large-scale genetic surveillance of malaria implemented by National Malaria Control Programmes informs public health decision makers about the spread of strains resistant to antimalarials.