Recent advances in genome editing of bloodstream forms of Trypanosoma congolense using CRISPR-Cas9 ribonucleoproteins: Proof of concept.

African Animal Trypanosomosis (AAT or Nagana) is a vector-borne disease caused by Trypanosomatidae, genus Trypanosoma. The disease is transmitted by the bite of infected hematophagous insects, mainly tsetse flies but also other blood-sucking insects including stomoxes and tabanids. Although many trypanosome species infect animals, the main agents responsible for this disease with a strong socio-economic and veterinary health impact are Trypanosoma congolense (T.

Alsinol, an arylamino alcohol derivative active against Plasmodium, Babesia, Trypanosoma, and Leishmania: past and new outcomes.

Malaria, babesiosis, trypanosomosis, and leishmaniasis are some of the most life-threatening parasites, but the range of drugs to treat them is limited. An effective, safe, and low-cost drug with a large activity spectrum is urgently needed. For this purpose, an aryl amino alcohol derivative called Alsinol was resynthesized, screened in silico, and tested against Plasmodium, Babesia, Trypanosoma, and Leishmania.

Mini-review on CRISPR-Cas9 and its potential applications to help controlling neglected tropical diseases caused by Trypanosomatidae.

The CRISPR-Cas system, which was originally identified as a prokaryotic defense mechanism, is increasingly being used for the functional study of genes. This technology, which is simple, inexpensive and efficient, has aroused a lot of enthusiasm in the scientific community since its discovery, and every month many publications emanate from very different communities reporting on the use of CRISPR-Cas9. Currently, there are no vaccines to control neglected tropical diseases (NTDs) caused by Trypanosomatidae, particularly Human African Trypanosomiasis (HAT) and Animal African Trypanosomoses (AAT), and treatments are cumbersome and sometimes not effective enough.

Development of a bead-based multiplexed assay for simultaneous quantification of five bovine cytokines by flow cytometry.

Quantifying cytokines is extremely important in studies of host-pathogen interactions. Multiplex assays are commercially available but only for human and mouse cytokines. Here a method for the simultaneous quantification of five important bovine cytokines IFNγ, IL-4, IL-10, IL-12, and TNFα in cell culture supernatants, using flow cytometry was reported.

A comparison of phenotypic traits related to trypanotolerance in five west african cattle breeds highlights the value of shorthorn taurine breeds.

Background: Animal African Trypanosomosis particularly affects cattle and dramatically impairs livestock development in sub-Saharan Africa. African Zebu (AFZ) or European taurine breeds usually die of the disease in the absence of treatment, whereas West African taurine breeds (AFT), considered trypanotolerant, are able to control the pathogenic effects of trypanosomosis. Up to now, only one AFT breed, the longhorn N'Dama (NDA), has been largely studied and is considered as the reference trypanotolerant breed.

Design and evaluation of a unique SYBR Green real-time RT-PCR assay for quantification of five major cytokines in cattle, sheep and goats.

Background: Today, when more than 60% of animal diseases are zoonotic, understanding their origin and development and identifying protective immune responses in ruminants are major challenges. Robust, efficient and cost-effective tools are preconditions to solve these challenges. Cytokines play a key role in the main mechanisms by which the immune system is balanced in response to infectious pathogens.

APOL1 expression is induced by Trypanosoma brucei gambiense infection but is not associated with differential susceptibility to sleeping sickness.

Most African trypanosome species are sensitive to trypanolytic factors (TLFs) present in human serum. Trypanosome lysis was demonstrated to be associated with apolipoprotein L-I (APOL1). Trypanosoma brucei (T.

A quasi-exclusive European ancestry in the Senepol tropical cattle breed highlights the importance of the slick locus in tropical adaptation.

Background: The Senepol cattle breed (SEN) was created in the early XX(th) century from a presumed cross between a European (EUT) breed (Red Poll) and a West African taurine (AFT) breed (N'Dama). Well adapted to tropical conditions, it is also believed trypanotolerant according to its putative AFT ancestry. However, such origins needed to be verified to define relevant husbandry practices and the genetic background underlying such adaptation needed to be characterized.

Intertwining threshold settings, biological data and database knowledge to optimize the selection of differentially expressed genes from microarray.

Background: Many tools used to analyze microarrays in different conditions have been described. However, the integration of deregulated genes within coherent metabolic pathways is lacking. Currently no objective selection criterion based on biological functions exists to determine a threshold demonstrating that a gene is indeed differentially expressed.

"Pathogeno-proteomics".

Many scientists working on pathogens (viruses, bacteria, fungi, parasites) are betting heavily on data generated by longitudinal genomic-transcriptomic-proteomic studies to explain biochemical host-vector-pathogen interactions and thus to contribute to disease control. Availability of genome sequences of various organisms, from viruses to complex metazoans, led to the discovery of the functions of the genes themselves. The postgenomic era stimulated the development of proteomic and bioinformatics tools to identify the locations, functions, and interactions of the gene products in tissues and/or cells of living organisms.

Bovine transcriptome analysis by SAGE technology during an experimental Trypanosoma congolense infection.

In central and sub-Saharan Africa, trypanosomosis is a tsetse fly-transmitted disease, which is considered as the most important impediment to livestock production in the region. However, several indigenous West African taurine breeds (Bos taurus) present remarkable tolerance to the infection. This genetic capability, named trypanotolerance, results from numerous biological mechanisms most probably under multigenic dependences, among which are control of the trypanosome infection by limitation of parasitemia and control of severe anemia due to the pathogenic effects.

Comparative genomic analysis of three strains of Ehrlichia ruminantium reveals an active process of genome size plasticity.

Ehrlichia ruminantium is the causative agent of heartwater, a major tick-borne disease of livestock in Africa that has been introduced in the Caribbean and is threatening to emerge and spread on the American mainland. We sequenced the complete genomes of two strains of E. ruminantium of differing phenotypes, strains Gardel (Erga; 1,499,920 bp), from the island of Guadeloupe, and Welgevonden (Erwe; 1,512,977 bp), originating in South Africa and maintained in Guadeloupe in a different cell environment.

Efficiency and limits of the Serial Analysis of Gene Expression (SAGE) method: discussions based on first results in bovine trypanotolerance.

Post genomic biotechnologies, such as transcriptome analysis, are now efficient enough to characterize the full complement of genes involved in the expression of specific biological functions. One of them is the Serial Analysis of Gene Expression (SAGE) technique. SAGE involves the construction of transcript libraries for a quantitative analysis of the entire set of genes expressed or inactivated at particular stages of cellular activation.

Selection assisted by a BoLA-DR/DQ haplotype against susceptibility to bovine dermatophilosis.

Bovine dermatophilosis is a severe skin infection of tropical ruminants inducing a severe loss in productivity and a 15% mortality rate. This disease is caused by the actinomycete bacterium Dermatophilus congolensis associated with the tick Amblyomma variegatum. Currently there are no prospects for a vaccine, and acaricide or antibiotic control is hampered by the development of chemoresistance.

Molecular immunogenetics in susceptibility to bovine dermatophilosis: a candidate gene approach and a concrete field application.

To identify molecular genetic markers of resistance or susceptibility to dermatophilosis in cattle, we used a functional candidate gene approach to analyze the DNA polymorphisms of targeted genes encoding molecules implicated in known mechanisms of both nonspecific and specific immune responses existing in the pathogen/host interface mechanisms. The most significant results were obtained within the Major Histocompatibility Complex (MHC) where the BoLA-DRB3 and DQB genes encode molecules involved in the antigen presentation to T cell receptors. A unique BoLA class II haplotype, made up of one DRB3 exon 2 allele and one DQB allele, highly correlates with the susceptibility character (P < 0.