Frontiers in Parasitology 

About: Frontiers in Parasitology is an academic journal. The journal publishes majorly in the area(s): Biology & Medicine. It has an ISSN identifier of 2813-2424. Over the lifetime, 30 publications have been published receiving 13 citations. The journal is also known as: Front Parasitol.

Immunomodulatory and biological properties of helminth-derived small molecules: Potential applications in diagnostics and therapeutics

Abstract: Parasitic helminths secrete and excrete a vast array of molecules known to help skew or suppress the host’s immune response, thereby establishing a niche for sustained parasite maintenance. Indeed, the immunomodulatory potency of helminths is attributed mainly to excretory/secretory products (ESPs). The ESPs of helminths and the identified small molecules (SM) are reported to have diverse biological and pharmacological properties. The available literature reports only limited metabolites, and the identity of many metabolites remains unknown due to limitations in the identification protocols and helminth-specific compound libraries. Many metabolites are known to be involved in host-parasite interactions and pathogenicity. For example, fatty acids (e.g., stearic acid) detected in the infective stages of helminths are known to have a role in host interaction through facilitating successful penetration and migration inside the host. Moreover, excreted/secreted SM detected in helminth species are found to possess various biological properties, including anti-inflammatory activities, suggesting their potential in developing immunomodulatory drugs. For example, helminths-derived somatic tissue extracts and whole crude ESPs showed anti-inflammatory properties by inhibiting the secretion of proinflammatory cytokines from human peripheral blood mononuclear cells and suppressing the pathology in chemically-induced experimental mice model of colitis. Unlike bigger molecules like proteins, SM are ideal candidates for drug development since they are small structures, malleable, and lack immunogenicity. Future studies should strive toward identifying unknown SM and isolating the under-explored niche of helminth metabolites using the latest metabolomics technologies and associated software, which hold potential keys for finding new diagnostics and novel therapeutics.

Comparison of molecular surveillance methods to assess changes in the population genetics of Plasmodium falciparum in high transmission

Abstract: A major motivation for developing molecular methods for malaria surveillance is to measure the impact of control interventions on the population genetics of Plasmodium falciparum as a potential marker of progress towards elimination. Here we assess three established methods (i) single nucleotide polymorphism (SNP) barcoding (panel of 24-biallelic loci), (ii) microsatellite genotyping (panel of 12-multiallelic loci), and (iii) varcoding (fingerprinting var gene diversity, akin to microhaplotyping) to identify changes in parasite population genetics in response to a short-term indoor residual spraying (IRS) intervention. Typical of high seasonal transmission in Africa, multiclonal infections were found in 82.3% (median 3; range 1-18) and 57.8% (median 2; range 1-12) of asymptomatic individuals pre- and post-IRS, respectively, in Bongo District, Ghana. Since directly phasing multilocus haplotypes for population genetic analysis is not possible for biallelic SNPs and microsatellites, we chose ~200 low-complexity infections biased to single and double clone infections for analysis. Each genotyping method presented a different pattern of change in diversity and population structure as a consequence of variability in usable data and the relative polymorphism of the molecular markers (i.e., SNPs < microsatellites < var). Varcoding and microsatellite genotyping showed the overall failure of the IRS intervention to significantly change the population structure from pre-IRS characteristics (i.e., many diverse genomes of low genetic similarity). The 24-SNP barcode provided limited information for analysis, largely due to the biallelic nature of SNPs leading to a high proportion of double-allele calls and a view of more isolate relatedness compared to microsatellites and varcoding. Relative performance, suitability, and cost-effectiveness of the methods relevant to sample size and local malaria elimination in high-transmission endemic areas are discussed.

Unravelling var complexity: Relationship between DBLα types and var genes in Plasmodium falciparum

Abstract: The enormous diversity and complexity of var genes that diversify rapidly by recombination has led to the exclusion of assembly of these genes from major genome initiatives (e.g., Pf6). A scalable solution in epidemiological surveillance of var genes is to use a small ‘tag’ region encoding the immunogenic DBLα domain as a marker to estimate var diversity. As var genes diversify by recombination, it is not clear the extent to which the same tag can appear in multiple var genes. This relationship between marker and gene has not been investigated in natural populations. Analyses of in vitro recombination within and between var genes have suggested that this relationship would not be exclusive. Using a dataset of publicly-available assembled var sequences, we test this hypothesis by studying DBLα-var relationships for four study sites in four countries: Pursat (Cambodia) and Mae Sot (Thailand), representing low malaria transmission, and Navrongo (Ghana) and Chikwawa (Malawi), representing high malaria transmission. In all study sites, DBLα-var relationships were shown to be predominantly 1-to-1, followed by a second largest proportion of 1-to-2 DBLα-var relationships. This finding indicates that DBLα tags can be used to estimate not just DBLα diversity but var gene diversity when applied in a local endemic area. Epidemiological applications of this result are discussed.

Identification of an in vitro artemisinin-resistant Plasmodium falciparum kelch13 R515K mutant parasite in Senegal

Abstract: The emergence of artemisinin partial resistance (ART-r) in Plasmodium falciparum malaria parasites has substantially compromised the efficacy of antimalarial treatments across southeast Asia (SE Asia). The spread of ART-r within the African continent could jeopardize past progress made in reducing worldwide malaria burden. A clinical index malaria case was identified in Kaolack, Senegal with persistent fever after complete artesunate-amodiaquine (ASAQ) treatment. Fifteen malaria-infected blood samples were collected by Institut Pasteur Dakar’s Senegalese sentinel surveillance system, from different healthcare centers surrounding the index case. We have identified one Plasmodium falciparum clinical isolate carrying R515K mutation in the artemisinin resistance gene PfKelch13. CRISPR-Cas9 genome editing was carried out and transgenic Pf3D7Pfkelch13R515K was tested for in vitro standard Ring-stage Survival Assay (RSA 0-3hpi). Gene editing has confirmed that PfKelch13R515K drove increased in vitro RSA0-3hpi value. In this article, we report the functional significance of PfKelch13R515K mutation in an African context.

The luminal domain of Toxoplasma gondii sortilin adopts a ring-shaped structure exhibiting motifs specific to apicomplexan parasites

Abstract: Rhoptries and micronemes are essential for host cell invasion and survival of all apicomplexan parasites, which are composed of numerous obligate intracellular protozoan pathogens including Plasmodium falciparum (malaria) and Toxoplasma gondii (toxoplasmosis) that infect humans and animals causing severe diseases. We identified Toxoplasma gondii TgSORT as an essential cargo receptor, which drives the transport of rhoptry (ROP) and microneme (MIC) proteins to ensure the biogenesis of these secretory organelles. The luminal domain of 752 amino acid long situated at the N-terminus end of TgSORT has been described to bind to MIC and ROP proteins. Here, we present an optimized protocol for expression of the entire luminal N-terminus of TgSORT (Tg-NSORT) in the yeast Pichia pastoris. Optimization of its coding sequence, cloning and transformation of the yeast P. pastoris allowed the secretion of Tg-NSORT. The protein was purified and further analyzed by negative staining electron microscopy. In addition, molecular modeling using AlphaFold identified key differences between the human and the T gondii sortilin. The structural features that are only present in T. gondii and other apicomplexan parasites were highlighted. Elucidating the roles of these specific structural features may be useful for designing new therapeutic agents against apicomplexan parasites