Interactions among multiple genomes: Tsetse, its symbionts and trypanosomes
Introduction
Tsetse flies (Diptera: Glossinidae) are the sole vectors of cyclical pathogenic trypanosomes in tropical Africa. Human African trypanosomiasis (HAT), or sleeping sickness, is a zoonosis caused by the flagellated protozoan Trypanosoma brucei rhodesiense in East and southern Africa and T. b. gambiense in West and Central Africa. It is conservatively estimated by the World Health Organization (WHO, 2001) that there are currently 300,000–500,000 cases of HAT with 60 million people at risk in 37 countries covering approximately 40% of Africa (11 M km2). After a devastating epidemic in the early 20th century when a million people died of HAT, the disease almost disappeared from Africa by the 1960s following eradication campaigns, mostly based on insecticide applications. But we are currently in the midst of another HAT epidemic with a high disease burden of 2.05 M disability-adjusted life years (Ekwanzala et al., 1996; Moore et al., 1999; van Hove, 1996). The countries in Central Africa, especially the Democratic Republic of Congo (DRC), Angola and Southern Sudan, are countries which have been the hardest hit while Uganda is under threat with sporadic infections reported. The rate of new infections and mortality (55,000 deaths in 1993; 66,000 in 1999) shows no sign of decline. The collapse of health infrastructures and surveillance systems (Simarro et al., 2003), allied to the displacement of populations by war and natural disaster, are important contributory factors to the present epidemic. Given that the disease affects hard-to-reach rural populations, which lack active surveillance in the war-torn areas, it is not surprising that the disease prevalence estimates are generally considered a gross underestimation. The consensus view is that the situation may worsen (Barrett, 1999; Smith et al., 1998; Stich et al., 2003). In addition to their importance to human health, trypanosomes cause a wasting and fatal disease in cattle, domestic pigs and other farm animals known as nagana. Nagana is caused by the related parasites, T. b. brucei, T. congolense and T. vivax and has restricted agricultural development and nutritional resources in sub-Saharan Africa profoundly impacting the economy of much of the continent (Jordan, 1986; Steelman, 1976).
The prevalence of trypanosomiasis relies on four interacting organisms: the human host, the insect vector, the pathogenic parasite and the domestic and wild animal reservoirs. While complex, this dependence on multiple players provides several opportunities for intervention since interruption of any of these interactions can potentially reduce disease transmission. Despite extensive research on African trypanosomes in pursuit of vaccine candidates for the immunization of humans and cattle, antigenic variation of surface glycoproteins while in the mammalian host has hampered most efforts. Moreover, there are no effective vaccine candidates forthcoming for disease control in the foreseeable future. The current management of HAT has relied on the extensive involvement of international organizations and relies on active surveillance and treatment of infected patients. These efforts have been constrained by the lack of inexpensive, easy to administer and effective drugs (Butler, 2003; Docampo and Moreno, 2003). In addition, the efficacy of available drugs has been impaired due to increasing resistance by the parasites (Anene et al., 2001; Geerts et al., 2001). The soon to be completed genome sequence of the parasite now provides the impetus for the identification of new potential targets of attack (El-Sayed et al., 2003). Nevertheless, strategic difficulties in accessing the rural populations inflicted with this disease, the lack of sensitive diagnostic tools and the presence of extensive wild animal reservoirs for the parasite will continue to threaten the long-term success of chemotherapy as the gold-standard for control of this particular disease.
Section snippets
Tsetse—vector of African trypanosomes
Tsetse flies, both the blood-feeding males and females, are the sole vectors of human-infective African trypanosomes. The major human disease vectors are species of the palpalis complex, involved in transmission of T. b. gambiense in Central and West Africa and T. b. rhodesiense in East Africa, although flies of the morsitans complex also contribute to significant human disease transmission (recently reviewed in Aksoy et al., 2003). For T. b. rhodesiense, the presence of domestic and wild
Symbiosis in tsetse
Arthropods, in particular, owe much of their ecological success to resident microbial flora that often provide nutrients either lacking in their limited diet or which the hosts are incapable of synthesizing (Table 1). Symbiotic associations allow the hosts to exploit unique or restricted ecological niches that would otherwise be impractical to inhabit. Symbionts with obligate functions in host biology have been termed primary (P)-symbionts, while the more recently established commensal-like
Symbiont transformation technology
Although the microaerophilic nature of many gut symbionts has hampered their cultivation from animals, Sodalis has been successfully cultivated in vitro (Welburn et al., 1987; Beard et al., 1993). The availability of an in vitro culture system has enabled the development of a genetic transformation system to introduce and express foreign products in Sodalis (Beard et al., 1993) and, in turn in their host insects, an approach called paratransgenesis (Aksoy, 2001; Aksoy, 2003; Aksoy et al., 2001;
Gene-driving systems—Wolbachia-mediated cytoplasmic incompatability
An important applied aspect of all transgenic approaches is the ability to spread the laboratory-engineered phenotypes into natural populations. The Wolbachia symbiont which has infected a wide range of invertebrate hosts (Werren et al., 1995), including several tsetse species, provides one potential drive mechanism. One of the unique functions of Wolbachia, termed cytoplasmic incompatibility (CI), results in death early in embryogenesis. In an incompatible cross, the sperm enters the egg but
Conclusions and future directions
Extensive knowledge accumulated on tsetse and its symbionts now provides unique disease management opportunities based on the control of parasite development in its invertebrate host. Both symbionts Wigglesworthia and Sodalis display genomic traits reflective of their dependencies on their host biology. Their close proximity to the developing trypanosomes in the gut, the ease of prokaryotic transformation systems and gene expression, as well as the soon available genome sequence information
Acknowledgements
We are grateful to past and present members of our group, Xiao-ai Chen, Song Li, Quiying Cheng, Jian Yan, Leyla Akman, Zhengrong Hao, Youjia Hu, Irene Kasumba, Dana Nayduch, Brian Weiss, Douglas Smith and Patricia M. Strickler and to colleagues Masahira Hattori, Hidemi Watanabe, Atsushi Yamashita and Hattori Toh for their contributions to this work. We are grateful to the agencies NIH/NIAID, NSF, WHO as well as to the Li Foundation and MacKnight Foundation, Robert Leet and Clara Gutherie
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2022, Journal of Invertebrate PathologyCitation Excerpt :To fill these gaps in understudied ecological settings, PCR-based method was used to identify S. glossinidius and Wolbachia in wild population of G. m. submorsitans caught in the area of Lake Iro in the south of Chad. The identification of S. glossinidius and Wolbachia in wild population of G. m. submorsitans of Lake Iro is in line with previous studies that reported these two symbiotic micro-organisms in wild populations of G. m. morsitans, G. tachinoides, G. p. palpalis, G. pallidipes, G. f. quanzensis and G. brevipalpis (Aksoy and Rio, 2005; Dennis et al., 2014; Alam et al., 2011; Kante et al., 2018b; Kame-Ngasse et al., 2018; Simo et al., 2019). The S. glossinidius infection rate of 9.0% obtained in the present study is similar to 9.3% reported in Liberia for G. p. palpalis (Maudlin et al., 1999).
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2014, Advances in GeneticsPrevalence and genetic variation of salivary gland hypertrophy virus in wild populations of the tsetse fly Glossina pallidipes from southern and eastern Africa
2013, Journal of Invertebrate PathologyCitation Excerpt :Both diseases have profound impacts on the health of livestock and humans, agricultural development and nutritional resources in sub-Saharan Africa (Jordan, 1986). Due to a lack of effective vaccines and inexpensive drugs for HAT and development of drug resistance for AAT (Aksoy and Rio, 2005), vector control remains the most feasible strategy for the sustainable management of these diseases. The successful eradication of Glossina austeni from the Island of Unguja, United Republic of Tanzania, using an area-wide integrated pest management approach (AW-IPM) (Hendrichs et al., 2007) including the release of sterile male tsetse flies (Vreysen et al., 2000) in 1994–1997, lead the Government of Ethiopia to embark on a program to eradicate Glossina pallidipes from the Southern Rift Valley (Feldmann et al., 2005).
Global Wolbachia prevalence, titer fluctuations and their potential of causing cytoplasmic incompatibilities in tsetse flies and hybrids of Glossina morsitans subgroup species
2013, Journal of Invertebrate PathologyCitation Excerpt :For example, these α-proteobacteria are capable of triggering a diverse repertoire of life-history traits in insects such as cytoplasmic incompatibility (CI), sex ratio distortion, longevity, innate immunity, locomotion, olfaction, toxin-sensitivity as well as sexual mating behavior changes (recently reviewed in Schneider et al. (2010)). Wolbachia are, next to the γ-proteobacteria Sodalis glossinidius and Wigglesworthia glossinida, part of the triple-symbiont association present in tsetse flies (reviewed in Aksoy and Rio (2005)). Over the last years, numerous studies have focused on the complex interactions exhibited between tsetse flies and their symbionts (Aksoy and Rio, 2005).
Pathogenic mechanisms of Trypanosoma evansi infections
2012, Research in Veterinary ScienceCitation Excerpt :It is conservatively estimated by the World Health Organization (WHO, 2001) that there are currently 300,000–500,000 cases of which 60 million people are at risk in 37 countries covering approximately 40% of Africa (11 Mkm2). The rate of new infections and mortality (55,000 deaths in 1993; 66,000 in 1999) shows no sign of decline (Aksoy and Rio, 2005). In addition to their importance to human health, trypanosomes cause a wasting and fatal disease in cattle, domestic pigs and other farm animals known as Nagana (Aksoy, 2003).