a b s t r a c tThe 2-C-methyl-D-erythritol-4-phosphate and shikimate pathways were found to be active in Plasmodium falciparum and both can result in vitamin E biosynthesis in plants and algae. This study biochemically confirmed vitamin E biosynthesis in the malaria parasite, which can be inhibited by usnic acid. Furthermore, we found evidence pointing to a role of this vitamin in infected erythrocytes. These findings not only contribute to current understanding of P. falciparum biology but also reveal a pathway that could serve as a chemotherapeutic target.

Herein, we show that intraerythrocytic stages of Plasmodium falciparum have an active pathway for biosynthesis of menaquinone. Kinetic assays confirmed that plasmodial menaquinone acts at least in the electron transport. Similarly to Escherichia coli, we observed increased levels of menaquinone in parasites kept under anaerobic conditions. Additionally, the mycobacterial inhibitor of menaquinone synthesis Ro 48-8071 also suppressed menaquinone biosynthesis and growth of parasites, although off-targets may play a role in this growth-inhibitory effect. Due to its absence in humans, the menaquinone biosynthesis can be considered an important drug target for malaria.

Background Plasmodium falciparum is sensitive to oxidative stress in vitro and in vivo, and many drugs such as artemisinin, chloroquine and cercosporin interfere in the parasite’s redox system. To minimize the damage caused by reactive radicals, antioxidant enzymes and their substrates found in parasites and in erythrocytes must be functionally active. It was shown that P. falciparum synthesizes vitamin E and that usnic acid acts as an inhibitor of its biosynthesis. Vitamin E is a potent antioxidant that protects polyunsaturated fatty acids from lipid peroxidation, and this activity can be measured by detecting its oxidized product and by evaluating reactive oxygen species (ROS) levels.ResultsHere, we demonstrated that ROS levels increased in P. falciparum when vitamin E biosynthesis was inhibited by usnic acid treatment and decreased to basal levels if exogenous vitamin E was added. Furthermore, we used metabolic labelling to demonstrate that vitamin E biosynthesized by the parasite acts as an antioxidant since we could detect its radiolabeled oxidized product. The treatment with chloroquine or cercosporin of the parasites increased the ratio between α-tocopherolquinone and α-tocopherol.ConclusionsOur findings demonstrate that vitamin E produced endogenously by P. falciparum is active as an antioxidant, probably protecting the parasite from the radicals generated by drugs.Electronic supplementary materialThe online version of this article (10.1186/s13071-017-2402-3) contains supplementary material, which is available to authorized users.

Leishmaniasis is a neglected disease caused by a trypanosomatid protozoan of the genus Leishmania. Most drugs used to treat leishmaniasis are highly toxic, and the emergence of drug‐resistant strains has been observed. Therefore, new therapeutic targets against leishmaniasis are required. Several isoprenoid compounds, including dolichols or ubiquinones, have been shown to be important for cell viability and proliferation in various trypanosomatid species. Here, we detected the biosynthesis of tocopherol in Leishmania (L.) amazonensis promastigotes in vitro through metabolic labelling with [1‐(n)‐3H]‐phytol. Subsequently, we confirmed the presence of vitamin E in the parasite by gas chromatography–mass spectrometry. Treatment with usnic acid or nitisinone, inhibitors of precursors of vitamin E synthesis, inhibited growth of the parasite in a concentration‐dependent manner. This study provides the first evidence of tocopherol biosynthesis in a trypanosomatid and suggests that inhibitors of the enzyme 4‐hydroxyphenylpyruvate dioxygenase may be suitable for use as antileishmanial compounds. Database The amino acid sequence of a conserved hypothetical protein [Leishmania mexicana MHOM/GT/2001/U1103] has been deposited in GenBank ()

Malaria, an infectious disease that kills more than 438,000 people per year worldwide, is a major public health problem. The emergence of strains resistant to conventional therapeutic agents necessitates the discovery of new drugs. We previously demonstrated that various substances, including terpenes, have antimalarial activity in vitro and in vivo. Nerolidol is a sesquiterpene present as an essential oil in several plants that is used in scented products and has been approved by the US Food and Drug Administration as a food-flavouring agent. In this study, the antimalarial activity of nerolidol was investigated in a mouse model of malaria. Mice were infected with Plasmodium berghei ANKA and were treated with 1000 mg/kg/dose nerolidol in two doses delivered by the oral or inhalation route. In mice treated with nerolidol, parasitaemia was inhibited by >99% (oral) and >80% (inhalation) until 14 days after infection (P <0.0001). On Day 30 post-infection, the survival rate of orally treated mice was 90% compared with 16% in controls (P <0.0001). In contrast, inhalation-treated mice showed a survival rate of 50% vs. 42% in controls (P > 0.05). The toxicity of nerolidol administered by either route was not significant, whilst genotoxicity was observed only at the highest dose tested. These results indicate that combined use of nerolidol and other drugs targeting different points of the same isoprenoid pathway may be an effective treatment for malaria.

Human parasitic protozoa cause a large number of diseases worldwide and, for some of these diseases, there are no effective treatments to date, and drug resistance has been observed. For these reasons, the discovery of new etiological treatments is necessary. In this sense, parasitic metabolic pathways that are absent in vertebrate hosts would be interesting research candidates for the identification of new drug targets. Most likely due to the protozoa variability, uncertain phylogenetic origin, endosymbiotic events, and evolutionary pressure for adaptation to adverse environments, a surprising variety of prenylquinones can be found within these organisms. These compounds are involved in essential metabolic reactions in organisms, for example, prevention of lipoperoxidation, participation in the mitochondrial respiratory chain or as enzymatic cofactors. This review will describe several prenylquinones that have been previously characterized in human pathogenic protozoa. Among all existing prenylquinones, this review is focused on ubiquinone, menaquinone, tocopherols, chlorobiumquinone, and thermoplasmaquinone. This review will also discuss the biosynthesis of prenylquinones, starting from the isoprenic side chains to the aromatic head group precursors. The isoprenic side chain biosynthesis maybe come from mevalonate or non-mevalonate pathways as well as leucine dependent pathways for isoprenoid biosynthesis. Finally, the isoprenic chains elongation and prenylquinone aromatic precursors origins from amino acid degradation or the shikimate pathway is reviewed. The phylogenetic distribution and what is known about the biological functions of these compounds among species will be described, as will the therapeutic strategies associated with prenylquinone metabolism in protozoan parasites.

O saneamento ambiental é instrumento essencial para a manutenção da qualidade ambiental, bem-estar e saúde humana. O estudo da percepção ambiental pode fornecer instrumentos para superar impasses relacionados a essa temática, pois proporciona uma tomada de consciência das problemáticas ligadas ao ambiente vivido. Deste modo, o objetivo desse trabalho foi analisar a percepção ambiental dos moradores da vila histórica de Caraíva, Porto Seguro-BA quanto a qualidade da água utilizada, impactos na saúde, responsabilidades e expectativas para melhorias, na perspectiva de contribuir com informações que possam subsidiar ações que propiciem melhores condições de vida para a população local. Para isso, foram realizadas 77 entrevistas através de roteiro estruturado com questões abertas e fechadas e observações em campo entre novembro de 2019 e março de 2020. Os dados qualitativos foram interpretados e analisados através da técnica do Discurso do Sujeito Coletivo (DSC). Com auxílio do software estatístico RStudio, os dados foram submetidos ao teste qui-quadrado para verificar se há relação de dependência entre variáveis sociodemográficas e resultados qualitativos. Foi constatado que a população depende acentuadamente da água dos poços rasos individuais, sendo esta fonte mais utilizada que a encanada da rede pública. A insegurança quanto a qualidade da água reflete na alta adesão por água mineral envasada. A escolaridade foi o fator de maior peso quanto a percepção de que água imprópria possa colocar a saúde em risco. Os entrevistados reconhecem a responsabilidade do poder público tanto para a manutenção dos serviços de fornecimento da água, quanto pela conservação da sua qualidade.    Enviromental perception regarding the quality of the water used in the historic village of Caraíva, Porto Seguro - BAA B S T R A C TEnvironmental sanitation represents an essential tool for maintaining environmental quality, well-being, and human health. The study of environmental perception, on the other hand, can provide instruments to overcome impasses related to this theme by providing an awareness of the problems related to the lived environment. This work aims to analyze the environmental perception of the historic village of Caraíva residents, in Porto Seguro, state of Bahia, Brazil regarding the quality of water used, health impacts, responsibilities, and expectations for improvements, It can also contribute with information to support actions that collaborate to provide better living conditions for the local population. For this purpose, 77 interviews were conducted through a structured script with open and closed questions and field observation between November 2019 and March 2020. Qualitative data were interpreted and through the technique of the Collective Subject Discourse (DSC). With the RStudio statistical software aid, the chi-square test was applied in the data to verify a dependency relationship between sociodemographic variables and qualitative results. According to the results, the population depends heavily on wells' water, and this water source is used more than a piped one. The insecurity regarding the water quality is reflected in the high adhesion to bottled mineral water. Schooling was the most significant factor in the perception that filtered water can put health at risk. Respondents recognize the public authorities' responsibility for maintaining water supply services and conserving their quality.Keywords: water resources management, environmental health, environmental impacts, environmental sanitation.

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