Interspecies and Intrastrain Interplay among Leishmania spp. Parasites.

Leishmania parasites present astonishing adaptative abilities that represent a matter of life or death within disparate environments during the heteroxenous parasite life cycle. From an evolutionary perspective, organisms develop methods of overcoming such challenges. Strategies that extend beyond the genetic diversity have been discussed and include variability between parasite cells during the infections of their hosts. The occurrence of Leishmania subpopulation fluctuations with variable structural genomic contents demonstrates that a single strain might shelter the variability required to overcome inconsistent environments. Such intrastrain variability provides parasites with an extraordinary ability to adapt and thus survive and propagate. However, different perspectives on this evolution have been proposed. Strains or species living in the same environment can cooperate but also compete. These interactions might increase the replication rate of some parasites but cause the loss of more aggressive competitors for others. Adaptive responses to intra- and interspecific competition can evolve as a fixed strategy (replication is adapted to the average genetic complexity of infections) or an optional strategy (replication varies according to the genetic complexity of the current infection). This review highlights the complexity of interspecies and intrastrain interactions among Leishmania parasites as well as the different factors that influence this interplay.

Leishmaniasis treatment: update of possibilities for drug repurposing.

The leishmaniases represent a public health problem in under-developed countries and are considered a neglected disease by the World Health Organization (WHO). They are cuased by Leishmania  parasites with different clinical manifestations. Currently, there is no vaccine, and treatment is in-efficient and is associated with both serious side effects often leading to resistance to the parasites. Thus, it is essential to search for new treatment strategies, such as drug repurposing, i.e., the use of drugs that are already used for other diseases. The discovery of new clinical applications for approved drugs is strategic for lowering the cost of drug discovery since human toxicity assays are already conducted. Here, we review a broad analysis of the different aspects of this approach for anti-leishmanial treatment.

Imipramine alters the sterol profile in Leishmania amazonensis and increases its sensitivity to miconazole.

BACKGROUND: Imipramine, a tricyclic antidepressant widely used clinically, has other pharmacological effects, such as antileishmanial activity. Tricyclic antidepressants interact with lipid bilayers, and some studies have shown that imipramine inhibits methyltransferases. Leishmania spp. produces compounds with an ergostane skeleton instead of a cholesterol skeleton, and the inhibition of enzymes of the sterol biosynthesis pathway is an interesting therapeutic target. Among these enzymes, C-24 methyltransferase has been suggested to play an essential role, as its inhibition kills the parasites. In this context, we investigated whether imipramine alters the biosynthesis of sterols in L. amazonensis and evaluated the efficacy of imipramine alone and in combination with miconazole, a classical inhibitor of another step in this pathway. METHODS: To analyze the interference of imipramine with sterol metabolism, promastigotes of L. amazonensis were cultured with medium alone, 15 or 30 µM imipramine or 4 µM miconazole, and their lipids were extracted with methanol/chloroform/water (1:0.5:0.4 v/v) and analyzed by GC/MS. To assess the antileishmanial activity of the treatments, promastigotes of L. amazonensis were incubated with various concentrations of imipramine up to 100 µM and up to 24 µM miconazole. Promastigotes were also treated with the combination of imipramine and miconazole at concentrations up to 12.5 µM of imipramine and 24 µM of miconazole. Parasite growth was evaluated by the MTT assay. The fractional inhibitory concentration index (FICI) was calculated to determine whether there were synergistic effects. Peritoneal macrophages with and without L. amazonensis infection were treated with miconazole (0 - 16 µM) or imipramine (0 to 50 µM) for 72 hours. For assays of the combined treatment in amastigotes, the concentration of imipramine was fixed at 12.5 µM and various concentrations of miconazole were used up to 16 µM. The infection rate was determined by counting the infected macrophages under a light microscope. FINDINGS: Promastigotes treated with imipramine accumulated cholesta-5,7,22-trien-3ß-ol and cholesta-7-24-dien- 3ß-ol, sterols that normally increase after treatment with classical inhibitors of C-24 methyltransferase. The IC50 of miconazole in promastigotes decreased when it was used in combination with imipramine, resulting in an additive effect, with a FICI value of 0.83. Imipramine also showed activity against intracellular amastigotes and enhanced the activity of miconazole, without apparent toxicity to the host cells. CONCLUSIONS: Imipramine was confirmed to have antileishmanial activity in both forms of the parasite, affecting the sterol biosynthesis of the organisms. Using imipramine in combination with azoles may be advantageous for the treatment of leishmaniasis.

Absence of angiostrongylid nematodes in wild non-flying small mammals in Duas Bocas Biological Reserve, Cariacica, southeastern Brazil

Uma busca por angiostrongilídeos foi realizada em cortes histológicos de vísceras provenientes de 129 pequenos mamíferos não voadores capturados na Reserva Biológica de Duas Bocas, município de Cariacica, Espírito Santo, Brasil. Não foram encontrados vermes ntra-arteriais. Dentro da árvore brônquica de dois indivíduos, identificados como Metachirus nudicaudatus e Didelphis aurita foram encontrados vermes cilíndricos, provavelmente filarídeos. Infecção humana, tanto por Angiostrongylus costaricensis quanto por Angiostrongylus cantonensis, já foi registrada no Espírito Santo inclusive nesta região de Cariacica, porém não há dados sobre a infecção natural em outros mamíferos. Este relato trata de uma tentativa pioneira de identificar angiostrongilídeos em animais coletados em uma Reserva Biológica no Estado do Espírito Santo.