Lysine lactylation has been recognized as a novel post-translational modification occurring on histones. However, lactylation in non-histone proteins, especially in proteins of early branching organisms, is not well understood. Energy metabolism and the histone repertoire in the early diverging protozoan parasite Trypanosoma brucei, the causative agent of African trypanosomiasis, markedly diverge from those of conventional eukaryotes. Here, we present the first exhaustive proteome-wide investigation of lactylated sites in T. brucei. We identified 387 lysine-lactylated sites in 257 proteins of various cellular localizations and biological functions. Further, we revealed that glucose metabolism critically regulates protein lactylation in T. brucei although the parasite lacks lactate dehydrogenase. However, unlike mammals, increasing the glucose concentration reduced the level of lactate, and protein lactylation decreased in T. brucei via a unique lactate production pathway. In addition to providing a valuable resource, these foregoing data reveal the regulatory roles of protein lactylation of trypanosomes in energy metabolism and gene expression.

Malaria, caused by Plasmodium parasites and transmitted by Anopheles mosquitoes, greatly impacts public health and socioeconomic development, particularly in sub-Saharan African countries. Despite advances in malaria treatment and prevention, the number of clinical cases and deaths have increased in recent years. The complex life cycle and genetic diversity of Plasmodium parasites pose significant challenges in drug and vaccine development, particularly due to the emerging partial resistance of parasites to artemisinin. With the availability and application of state-of-the-art biotechnology in recent years, knowledge in terms of parasite biology, pathogenicity, host–parasite interactions and pathogenesis has advanced tremendously. This review highlights the most recent research progress and understanding in Plasmodium biology, with a primary focus on P. falciparum and associated pathogenesis. The therapeutic targets and progress in the clinical application of anti-malaria drugs have also been summarized. The FDA-approved regimens like Artemether-Lumefantrine, Atovaquone-Proguanil, and Primaquine are discussed, and their benefits and limitations are highlighted, especially in terms of drug resistance. Perspectives in the development of novel vaccines and new drugs, such as Sevuparin, Imatinib, and Cipargamin, and combination therapies with promise in overcoming resistance has been proposed. Overall, this review provides a detailed summary of the latest progress in malaria research and emphasizes the need for continuous monitoring and innovation in malaria treatment.

The biology of Toxoplasma gondii, the causative pathogen of one of the most widespread parasitic diseases (toxoplasmosis), remains poorly understood. Lactate, which is derived from glucose metabolism, is not only an energy source in a variety of organisms, including T. gondii, but also a regulatory molecule that participates in gene activation and protein function. Lysine lactylation (Kla) is a type of post-translational modifications (PTMs) that has been recently associated with chromatin remodeling; however, Kla of histone and non-histone proteins has not yet been studied in T. gondii. To examine the prevalence and function of lactylation in T. gondii parasites, we mapped the lactylome of proliferating tachyzoite cells and identified 1964 Kla sites on 955 proteins in the T. gondii RH strain. Lactylated proteins were distributed in multiple subcellular compartments and were closely related to a wide variety of biological processes, including mRNA splicing, glycolysis, aminoacyl-tRNA biosynthesis, RNA transport, and many signaling pathways. We also performed a chromatin immunoprecipitation sequencing (ChIP-seq) analysis using a lactylation-specific antibody and found that the histones H4K12la and H3K14la were enriched in the promoter and exon regions of T. gondii associated with microtubule-based movement and cell invasion. We further confirmed the delactylase activity of histone deacetylases TgHDAC2–4, and found that treatment with anti-histone acetyltransferase (TgMYST-A) antibodies profoundly reduced protein lactylation in T. gondii. This study offers the first dataset of the global lactylation proteome and provides a basis for further dissecting the functional biology of T. gondii.

Proteins of all living cells undergo a myriad of post-translational modifications (PTMs) that are critical to multifarious life processes. In this study, we describe the first comprehensive multiple PTM-omics atlas in parallel with quantitative proteome analyses of two representative species of African trypanosomes, Trypanosoma brucei and Trypanosoma evansi. Ten PTM types with approximately 40,000 modified sites and 150 histone marks with a fine map on each protein of the two African trypanosomes were accomplished. The two biologically different trypanosomal species displayed distinct PTM-omic features, regulation pathways, and networks. Modifications in the proteins involved in the redox system were mainly upregulated in T. brucei, whereas proteins associated with motility were predominantly modified in T. evansi. The establishment of a database of multiple PTMs in the two parasites provides us with a deep insight into the biological mechanisms that underpin life processes in trypanosomes with different life cycles.

Toxoplasma gondii is a unicellular protozoan parasite of the phylum Apicomplexa. The parasite repeatedly goes through a cycle of invasion, division and induction of host cell rupture, which is an obligatory process for proliferation inside warm-blooded animals. It is known that the biology of the parasite is controlled by a variety of mechanisms ranging from genomic to epigenetic to transcriptional regulation. In this study, we investigated the global protein posttranslational lysine crotonylation and 2-hydroxyisobutyrylation of two T. gondii strains, RH and ME49, which represent distinct phenotypes for proliferation and pathogenicity in the host. Proteins with differential expression and modification patterns associated with parasite phenotypes were identified. Many proteins in T. gondii were crotonylated and 2-hydroxyisobutyrylated, and they were localized in diverse subcellular compartments involved in a wide variety of cellular functions such as motility, host invasion, metabolism and epigenetic gene regulation. These findings suggest that lysine crotonylation and 2-hydroxyisobutyrylation are ubiquitous throughout the T. gondii proteome, regulating critical functions of the modified proteins. These data provide a basis for identifying important proteins associated with parasite development and pathogenicity.