In vivo transcriptional profiling of Plasmodium falciparum

BACKGROUND: Both host and pathogen factors contribute to disease outcome in Plasmodium falciparum infection. The feasibility of studying the P. falciparum in vivo transcriptome to understand parasite transcriptional response while it resides in the human host is presented. METHODS: A custom made oligonucleotide array with probes based on the P. falciparum 3D7 laboratory strain chromosome 2 sequence was used to detect in vivo P. falciparum transcripts. This study analyzed transcripts from total RNA derived from small blood samples of P. falciparum infected patients and compared the in vivo expression profile to the in vitro cultivated 3D7 strain transcriptome. RESULTS: The data demonstrated that in vivo transcription can be studied from a small blood sample, despite the abundance of human RNA. The in vivo transcriptome is similar to the 3D7 ring stage transcriptome, but there are significant differences in genes encoding a sexual stage antigen and surface proteins. CONCLUSIONS: Whole genome transcription analysis of P. falciparum can be carried out successfully and further studies in selected patient cohorts may provide insight into parasite in vivo biology and defense against host immunity

Genetic structure and diversity in Sorghum bicolor (L.) Moench landraces from marginal sorghum production lands in Senegal, based on SSR markers

Data on sorghum genetic diversity in Senegal are missing despite its importance in the food and feed in the country. In order to contribute to the sustainable in situ management of sorghum germplasm, we investigated its genetic diversity and structure in its marginal production areas. Investigations were focused on Thiès, Diourbel and Kédougou regions where sorghum landraces have been less investigated and genetic information on landraces is unknown. A total of 148 sorghum accessions representative of landraces used in production systems have been sampled and analyzed with 30 microsatellite markers. A total of 138 alleles have been recorded. The number of alleles per locus varied from 3 (7 loci) to 8 (3 loci). The observed heterozygosity varied from 0 to 0.62. The low genetic distance (0.12) was recorded between Thiès and Diourbel populations and the highest distance (0.22) between Thiès and Kédougou populations. Dendrogram obtained according to Neighbour joining classification model allowed the classification of sorghum accessions into three main groups. The Genetic structure is not function to the regions indicating that landraces are not specific to a region. The results are a first step toward the sustainable in situ management of genetic resources. Data on the whole range of existing diversity of sorghum in Senegal is an important key for its germplasm management; so, the genotyping must be extended to accessions from the whole country

A Systematic Map of Genetic Variation in Plasmodium falciparum

Discovering novel genes involved in immune evasion and drug resistance in the human malaria parasite, Plasmodium falciparum, is of critical importance to global health. Such knowledge may assist in the development of new effective vaccines and in the appropriate use of antimalarial drugs. By performing a full-genome scan of allelic variability in 14 field and laboratory strains of P. falciparum, we comprehensively identified ≈500 genes evolving at higher than neutral rates. The majority of the most variable genes have paralogs within the P. falciparum genome and may be subject to a different evolutionary clock than those without. The group of 211 variable genes without paralogs contains most known immunogens and a few drug targets, consistent with the idea that the human immune system and drug use is driving parasite evolution. We also reveal gene-amplification events including one surrounding pfmdr1, the P. falciparum multidrug-resistance gene, and a previously uncharacterized amplification centered around the P. falciparum GTP cyclohydrolase gene, the first enzyme in the folate biosynthesis pathway. Although GTP cyclohydrolase is not the known target of any current drugs, downstream members of the pathway are targeted by several widely used antimalarials. We speculate that an amplification of the GTP cyclohydrolase enzyme in the folate biosynthesis pathway may increase flux through this pathway and facilitate parasite resistance to antifolate drugs

Ivermectin, ‘Wonder drug’ from Japan: the human use perspective

Discovered in the late-1970s, the pioneering drug ivermectin, a dihydro derivative of avermectin—originating solely from a single microorganism isolated at the Kitasato Intitute, Tokyo, Japan from Japanese soil—has had an immeasurably beneficial impact in improving the lives and welfare of billions of people throughout the world. Originally introduced as a veterinary drug, it kills a wide range of internal and external parasites in commercial livestock and companion animals. It was quickly discovered to be ideal in combating two of the world’s most devastating and disfiguring diseases which have plagued the world’s poor throughout the tropics for centuries. It is now being used free-of-charge as the sole tool in campaigns to eliminate both diseases globally. It has also been used to successfully overcome several other human diseases and new uses for it are continually being found. This paper looks in depth at the events surrounding ivermectin’s passage from being a huge success in Animal Health into its widespread use in humans, a development which has led many to describe it as a “wonder” drug