Biology subjects

Bengaly, Z.

Publications and source records attributed to Bengaly, Z..

3 recordsLinked to original sources

bioRxiv2021

Molecular epidemiology of Animal African Trypanosomosis in southwest Burkina Faso

BackgroundAnimal African Trypanosomosis (AAT) is a parasitic disease of livestock that has a major socio-economic impact in the affected areas. It is caused by several species of uniflagellate extracellular protists of the genus Trypanosoma mainly transmitted by tsetse flies: T. congolense, T. vivax and T. brucei brucei. In Burkina Faso, AAT hampers the proper economic development of the southwestern part of the country, which is yet the best watered area particularly conducive to agriculture and animal production. It was therefore important to investigate the extend of the infection in order to better control the disease. The objective of the present study was to assess the prevalence of trypanosome infections and collect data on the presence of tsetse flies. MethodsBuffy coat, Trypanosoma species-specific PCR, Indirect ELISA Trypanosoma sp and trypanolysis techniques were used on 1898 samples collected. An entomological survey was also carried out. ResultsThe parasitological prevalence of AAT was 1.1%, and all observed parasites were T. vivax. In contrast, the molecular prevalence was 23%, of which T. vivax was predominant (89%) followed by T. congolense (12%) and T. brucei s.l. (7.3%) with a sizable proportion as mixed infections (9.1%). T. brucei gambiense, responsible of sleeping sickness in humans, was not detected. The serological prevalence reached 49%. Once again T. vivax predominated (86.2%), but followed by T. brucei (9.6%) and T. congolense (4.2%), while 34.6% of positive samples tested positive for at least two trypanosome species. Seven samples, from six cattle and one pig, were found positive by trypanolysis. The density per trap of Glossina tachinoides and G. palpalis gambiensis was about three flies. Conclusions/SignificanceOverall, our study showed a high prevalence of trypanosome infection in the area, pointing out an ongoing inadequacy of control measures. Authors summaryIn Burkina Faso, like in most countries of sub-Saharan Africa, Animal African Trypanosomosis (AAT) is hampering economic development. It was therefore important to investigate the extent of trypanosome infections after years of control. This study examined circulating trypanosomes in domestic animals using parasitological, molecular and serological tools in southwest Burkina Faso. The prevalence levels observed show that the known epidemiological situation in the region has not really changed. The trypanosome species usually found in the area such as T. congolense, T. vivax and T. brucei s.l. have remained the same, with a stronger presence of T. vivax. The low occurrence of tsetse fly and the predominance of T. vivax attests to the role of the mechanical vectors in maintaining the disease. Although no cases of T. brucei gambiense infection was encountered in the animals examined, trypanolysis tests suggest that there are contact cases in this historical focus of sleeping sickness. Efforts are therefore necessary to reduce or even eliminate the trypanosome burden, and the data provided by this study can assist the decision making.

microbiology↗

bioRxiv2019

Variant antigen diversity in Trypanosoma vivax is not driven by recombination

African trypanosomes are vector-borne haemoparasites that cause African trypanosomiasis in humans and animals. Parasite survival in the bloodstream depends on immune evasion, achieved by antigenic variation of the Variant Surface Glycoprotein (VSG) coating the trypanosome cell surface. Recombination, or rather directed gene conversion, is fundamental in Trypanosoma brucei, as both a mechanism of VSG gene switching and of generating antigenic diversity during infections. Trypanosoma vivax is a related, livestock pathogen also displaying antigenic variation, but whose VSG lack key structures necessary for gene conversion in T. brucei. Thus, this study tests a long-standing prediction that T. vivax has a more restricted antigenic repertoire. Here we show that global VSG repertoire is broadly conserved across diverse T. vivax clinical strains. We use sequence mapping, coalescent approaches and experimental infections to show that recombination plays little, if any, role in diversifying T. vivax VSG sequences. These results explain interspecific differences in disease, such as propensity for self-cure, and indicate that either T. vivax has an alternate mechanism for immune evasion or else a distinct transmission strategy that reduces its reliance on long-term persistence. The lack of recombination driving antigenic diversity in T. vivax has immediate consequences for both the current mechanistic model of antigenic variation in African trypanosomes and species differences in virulence and transmission strategy, requiring us to reconsider the wider epidemiology of animal African trypanosomiasis.

microbiology↗

bioRxiv2018

The trypanocidal benzoxaborole AN7973 inhibits trypanosome mRNA processing

Kinetoplastid parasites - trypanosomes and leishmanias - infect millions of humans and cause economically devastating diseases of livestock, and the few existing drugs have serious deficiencies. Benzoxaborole-based compounds are very promising potential novel anti-trypanosomal therapies, with candidates already in human and animal clinical trials. Their targets in trypanosomes were hitherto unknown. We investigated the mechanism of action of several benzoxaboroles, including AN7973, an early candidate for veterinary trypanosomosis.\n\nIn all kinetoplastids, transcription is polycistronic. Individual mRNA 5-ends are created by trans splicing of a short leader sequence, with coupled polyadenylation of the preceding mRNA. Treatment of Trypanosoma brucei with AN7973 inhibited trans splicing within 1h, as judged by loss of the Y-structure splicing intermediate and reduced levels of mRNA, and accumulation of peri-nuclear granules which are typical for splicing inhibition. Methylation of the spliced leader precursor RNA was not affected, but more prolonged AN7973 treatment caused an increase in S-adenosyl methionine and methylated lysine. Together, these results indicate that mRNA processing is the primary target of AN7973. Polyadenylation is required for kinetoplastid trans splicing. The EC50 for AN7973 in T. brucei was increased three-fold by over-expression of the T. brucei cleavage and polyadenylation factor CPSF3, identifying CPSF3 as a potential molecular target. Our results thus chemically validate mRNA processing as a viable drug target in trypanosomes.\n\nSeveral other benzoxaboroles showed metabolomic and splicing effects that were similar to those of AN7973, identifying splicing inhibition as a common mode of action, and suggesting that it might be linked to subsequent changes in methylated metabolites. Granule formation, splicing inhibition, and resistance after CPSF3 expression did not, however, always correlate, and prolonged selection of trypanosomes in AN7973 resulted in only 1.5-fold resistance. This suggests that the modes of action of oxaboroles that target trypanosome mRNA processing may extend beyond CPSF3 inhibition.\n\nAuthor summaryTrypanosomes and leishmanias infect millions of humans and cause economically devastating diseases of livestock; the few existing drugs have serious deficiencies. Trypanosomosis of cattle, caused mainly by Trypanosoma congolense and Trypanosoma vivax, is a serious problem in Africa, because bovids are used not only for meat and milk, but also for traction. Only two drugs are in routine use for chemotherapy and chemoprophylaxis of bovine trypanosomosis. A single injection of the benzoxaborole compound AN7973 was sufficient to cure T. congolense infection in cattle and goats, but AN7973 was less effective against T. vivax. This precluded development of AN7973 as a commercially viable treatment against cattle trypanosomosis, but it could still have potential for diseases caused by other salivarian trypanosomes.\n\nWe used a large range of methods to find out how AN7973 kills trypanosomes, and compared it with several other benzoxaboroles. AN7973 and some of the other compounds had effects on parasite metabolism that resembled those previously seen for a benzoxaborole that is being tested for human sleeping sickness. The most rapid effect of AN7973, however, was on processing of trypanosome mRNA. As a consequence, amounts of mRNA decreased and synthesis of proteins stopped. We conclude that AN7973 and some other benzoxaboroles kill trypanosomes by stopping gene expression.

microbiology↗