Enhancing vector refractoriness to trypanosome infection: achievements, challenges and perspectives

Abstract

With the absence of effective prophylactic vaccines and drugs against African trypanosomosis, control of this group of zoonotic neglected tropical diseases depends the control of the tsetse fly vector. When applied in an area-wide insect pest management approach, the sterile insect technique (SIT) is effective in eliminating single tsetse species from isolated populations. The need to enhance the effectiveness of SIT led to the concept of investigating tsetse-trypanosome interactions by a consortium of researchers in a five-year (2013-2018) Coordinated Research Project (CRP) organized by the Joint Division of FAO/IAEA. The goal of this CRP was to elucidate tsetse-symbiome-pathogen molecular interactions to improve SIT and SIT-compatible interventions for trypanosomoses control by enhancing vector refractoriness. This would allow extension of SIT into areas with potential disease transmission. This paper highlights the CRP's major achievements and discusses the science-based perspectives for successful mitigation or eradication of African trypanosomosis.

Keywords: Glossina; Hytrosaviridae; Microbiota; Paratransgenesis; Trypanosoma-refractoriness, sterile insect technique; Vector competence.

Fig. 1

The tsetse fly and its associated microorganisms. Tsetse flies can harbor multiple microbes, including the bacterial endosymbionts obligate Wigglesworthia, facultative Sodalis, parasitic Wolbachia and Spiroplasma, as well as a taxonomically diverse population of environmentally acquired enteric bacteria, a virus (salivary gland hypertrophy virus, SGHV) and protozoan African trypanosomes. All tsetse harbor Wigglesworthia, while the presence of Sodalis, Wolbachia, Spiroplasma, SGHV and trypanosomes is fly population dependent. Wigglesworthia, Sodalis and SGHV are transmitted to developing intrauterine larval offspring via maternal milk secretions, while Wolbachia is transmitted through the germline. Spiroplasma’s mode of vertical transmission is currently unknown. Pathogenic trypanosomes are acquired by tsetse when they feed on an infected animal. The parasites must then undergo a complex development cycle in the fly before they can be successfully transmitted to a new host, where they cause disease. (This figure is adapted with permission from Aksoy et al., 2013) [179]

Fig. 2

Overview of the current status on tsetse paratransgenesis. Strategies have been developed for i) isolation and in vitro cultivation of Sodalis glossinidius, ii) establishing stable chromosomal expression in Sodalis allowing strong and constitutive expression of anti-trypanosome compounds in the absence of antibiotic selection and iii) the sustainable colonization of tsetse fly and its subsequent generations with genetically modified Sodalis through microinjection of the bacterium into third-instar larvae [; this issue]. Taken together, the necessary technology for application of Sodalis as a delivery system in tsetse paratransgenic has been developed, but the Sodalis-mediated inhibition of parasite development in the insect host is yet to be demonstrated. The final main bottleneck remains the identification of a highly potent and stable trypanolytic component effectively blocking parasite transmission by the fly without impairing symbiont and vector fitness