Here, an Anopheles stephensi mosquito is obtaining a blood meal from a human host through its pointed proboscis. Image credit: Centers for Disease Control and Prevention / Dr. William Collins.

This minireview series highlights recent developments in malaria research. The reviews cover diverse topics, from conventional antimalarial therapies and the strategies used to circumvent the emergence of drug resistance, to the latest approaches for the discovery and validation of new druggable targets and for the development of effective antimalarial vaccines.

Understanding the dynamic behaviour of the Plasmodium falciparum metabolism during infection can help identify targets for drug development. In this Commentary, we highlight recently published studies in The FEBS Journal that cover mathematical modelling of glycolysis in P. falciparum and the identification and in vivo validation of metabolic drug targets.

In this Commentary, we highlight the latest findings in three active areas of malaria research: Plasmodium biology; host response; and malaria control, prevention and treatment.

Malaria is caused by Plasmodium parasites and remains the most important mosquito-borne infectious disease. In this review, recent opportunities and persistent challenges for evidence-based malaria vaccine design are discussed. A better understanding of Plasmodium cell biology and immunology is essential to transform malaria into a vaccine-preventable disease.

Combating the spread of drug-resistant Plasmodium falciparum requires a comprehensive approach. Modern information technology provides the means to detect, enumerate, map and monitor cases of malaria resistance and the foci of transmission. Early detection and treatment of clinical cases, detection of submicroscopic reservoirs and adapted vector control are the three pillars of a successful elimination.

Malaria is characterized with oxidative stress derived from both the parasite's metabolism and the host immune response. Some antimalarial drugs increase oxidative stress. While oxidative stress can help eliminate parasites, it can also exacerbate the pathology. This article reviews oxidative stress in view of the current artemisinin-based combination therapies in malaria.

Plasmodium falciparum contains nearly 5400 genes and a multistage life cycle in humans and mosquitoes. Helicases are ATP-dependent nucleic acid unwinding enzymes. The P. falciparum genome analysis depicts that it contains some parasite-specific helicases and homologs to most of the human helicases. Here, an overview of P. falciparum helicases and their importance in parasite growth and survival is presented.

Proteases play a variety of biological functions in the malaria parasite. These include core biological processes such as protein homeostasis and traffic, but also parasite-specific functions (haemoglobin degradation, parasite egress, red blood cell invasion). This review provides an overview about the role of proteases in parasite development and outlines chemical and genetic strategies to validate proteases as therapeutic targets.

The sulfur mobilization (SUF) pathway of iron–sulfur [Fe–S] cluster assembly in the apicoplast of the malaria parasite has been delineated in this study. [4Fe–4S] clusters assembled on the SufBC₂D complex are transferred to targets via either NfU or SufA. Conditional knockout of SufS, the first enzyme of the pathway, demonstrates its essentiality in sporozoite development in the mosquito, providing support for SUF as a potential intervention site.

MSP2 from the malaria parasite Plasmodium falciparum induces a protective immune response. Tethering the conserved C-terminal region (MSP2_172–221) to liposomes induced an antigenic state that was more similar to the parasite antigen. Lipid-conjugated MSP2 may represent a useful vaccine formulation.

Formate-nitrite transporters (FNT) contain a substrate selectivity filter based on a lysine in a hydrophobic environment (Φ/K). It is reminiscent of the aquaporin aromatic/arginine region regarding composition, function, and location within the protein. Eukaryotic FNTs conduct lactate due to a funnel-shaped vestibule and a wide selectivity filter, whereas prokaryotic FNTs select for smaller substrates, mainly formate, nitrite, hydrosulfide, and acetate.

The eukaryotic genome replicates from multiple sites called origins. The genomic organization of these sites has been elusive in higher eukaryotes as well as in protozoan parasites. Here, we have identified and characterized the origins in Plasmodium falciparum by bioinformatic analysis and an experimental approach. An autocorrelation method was used to search for regions showing marked fluctuation or dips that may contain potential replication initiation sites. Finally the results of autocorrelation were verified experimentally.