The Diverse Calpain Family in Trypanosomatidae: Functional Proteins Devoid of Proteolytic Activity?

Calpains are calcium-dependent cysteine peptidases that were originally described in mammals and, thereafter, their homologues were identified in almost all known living organisms. The deregulated activity of these peptidases is associated with several pathologies and, consequently, huge efforts have been made to identify selective inhibitors. Trypanosomatids, responsible for life-threatening human diseases, possess a large and diverse family of calpain sequences in their genomes. Considering that the current therapy to treat trypanosomatid diseases is limited to a handful of drugs that suffer from unacceptable toxicity, tough administration routes, like parenteral, and increasing treatment failures, a repurposed approach with calpain inhibitors could be a shortcut to successful chemotherapy. However, there is a general lack of knowledge about calpain functions in these parasites and, currently, the proteolytic activity of these proteins is still an open question. Here, we highlight the current research and perspectives on trypanosomatid calpains, overview calpain description in these organisms, and explore the potential of targeting the calpain system as a therapeutic strategy. This review gathers the current knowledge about this fascinating family of peptidases as well as insights into the puzzle: are we unable to measure calpain activity in trypanosomatids, or are the functions of these proteins devoid of proteolytic activity in these parasites

Exploring the environmental diversity of kinetoplastid flagellates in the high-throughput DNA sequencing era

International audienceThe class Kinetoplastea encompasses both free-living and parasitic species from a wide range of hosts. Several representatives of this group are responsible for severe human diseases and for economic losses in agriculture and livestock. While this group encompasses over 30 genera, most of the available information has been derived from the vertebrate pathogenic genera Leishmania and Trypanosoma. Recent studies of the previously neglected groups of Kinetoplastea indicated that the actual diversity is much higher than previously thought. This article discusses the known segment of kinetoplastid diversity and how gene-directed Sanger sequencing and next-generation sequencing methods can help to deepen our knowledge of these interesting protists

Intestinal parasite infections in a rural community of Rio de Janeiro (Brazil): Prevalence and genetic diversity of <i>Blastocystis</i> subtypes

<div><p>Background</p><p>Intestinal parasitic infections are considered a serious public health problem and widely distributed worldwide, mainly in urban and rural environments of tropical and subtropical countries. Globally, soil-transmitted helminths and protozoa are the most common intestinal parasites. <i>Blastocystis</i> sp. is a highly prevalent suspected pathogenic protozoan, and considered an unusual protist due to its significant genetic diversity and host plasticity.</p><p>Methodology/main findings</p><p>A total of 294 stool samples were collected from inhabitants of three rural valleys in Rio de Janeiro, Brazil. The stool samples were evaluated by parasitological methods, fecal culture, nested PCR and PCR/Sequencing. Overall prevalence by parasitological analyses was 64.3% (189 out of 294 cases). <i>Blastocystis</i> sp. (55.8%) was the most prevalent, followed by <i>Endolimax nana</i> (18.7%), <i>Entamoeba histolytica</i> complex (7.1%), hookworm infection (7.1%), <i>Entomoeba coli</i> (5.8%), <i>Giardia intestinalis</i> (4.1%), <i>Iodamoeba butchilii</i> (1.0%), <i>Trichuris trichiura</i> (1.0%), <i>Pentatrichomonas hominis</i> (0.7%), <i>Enterobius vermicularis</i> (0.7%), <i>Ascaris lumbricoides</i> (0.7%) and <i>Strongyloides stercoralis</i> (0.7%). Prevalence of IPIs was significantly different by gender. Phylogenetic analysis of <i>Blastocystis</i> sp. and BLAST search revealed five different subtypes: ST3 (34.0%), ST1 (27.0%), ST2 (27.0%), ST4 (3.5%), ST8 (7.0%) and a non-identified subtype.</p><p>Conclusions/significance</p><p>Our findings demonstrate that intestinal parasite infection rates in rural areas of the Sumidouro municipality of Rio de Janeiro, Brazil are still high and remain a challenge to public health. Moreover, our data reveals significant genetic heterogeneity of <i>Blastocystis</i> sp. subtypes and a possible novel subtype, whose confirmation will require additional data. Our study contributes to the understanding of potential routes of transmission, epidemiology, and genetic diversity of <i>Blastocystis</i> sp. in rural areas both at a regional and global scale.</p></div

Distribution of intestinal parasites according to age groups and gender.

<p>Distribution of intestinal parasites according to age groups and gender.</p

Maximum likelihood (ML) and Bayesian inference (BI) trees based on the partial sequences of the partial SSU rDNA (437 bp) of <i>Blastocystis</i> sp. isolates of the present study.

<p>The high genetic divergence of rDNA gene revealed six clusters (denoted by ST1, 2, 3, 4, 8 and Novel-ST). The numbers along branches correspond to bootstrap values and Bayesian posterior probability values (values above 50% are shown) in the order: MP/BI.</p