Evolutionary genetics of tsetse and its symbionts
Principal Investigator: S Aksoy
Affiliation: Yale University
Abstract: DESCRIPTION (provided by applicant): Human African trypanosomiasis (HAT) kills thousands of people each year in sub-Saharan Africa. The disease is caused by African trypanosomes transmitted by the tsetse fly. HAT transmission is complex;it requires mammalian and invertebrate hosts and involves domestic and wild reservoirs. No mammalian vaccines exist and therapeutic drugs have serious side effects with increasing resistance seen in patients. In contrast, reduction of tsetse populations is highly efficacious for disease control. However, the implementation of the tsetse control programs, which rely on traps and targets, have been difficult to sustain because they are not practical and require extensive community participation. A paratransgenic strategy has been developed which exploits the unique biology of tsetse and its maternally inherited bacterial symbionts. In this strategy, tsetse's mutualist symbiont Sodalis is harnessed to express trypanosome inhibitory molecules in tsetse's midgut to impair trypanosome transmission. Transgenic Sodalis bacterium conferring refractoriness may be driven into natural tsetse populations by cytoplasmic incompatibility phenomenon mediated by tsetse's symbiont, Wolbachia. We propose to investigate the biogeography of the human disease vector species, Glossina fuscipes fuscipes, its Trypanosoma parasite(s), and its Wolbachia and Sodalis symbionts. Using a combination of laboratory and field experiments, we will investigate the potential for a Wolbachia mediated gene-drive mechanism to aid in the application of paratransgenic flies. In addition, we will elucidate the basic genetic structure of this human disease vector population, for which no information exists. This information is necessary for the efficacious implementation and monitoring of either the traditional or novel control strategies. Knowledge obtained on symbiont biology, maternal linkage of tsetse's multiple symbionts, Wolbachia infection phenotype, potential strength of Wolbachia mediated drive, population genetics and epidemiological dynamics will provide the parameters needed to develop a mathematically based model framework. This model will allow us to test the predictive nature of the empirical data, design the optimal strategies for population control, and predict feasibility and robustness for the success of the replacement strategy. This interdisciplinary application will combine epidemiology, population genetics and modeling with model parameterization and verification from laboratory and field research.
Funding Period: 2008-01-15 - 2012-12-31
more information: NIH RePORT
- Presence of extensive Wolbachia symbiont insertions discovered in the genome of its host Glossina morsitans morsitansCorey Brelsfoard
Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America Department of Natural Sciences, St Catharine College, St Catharine, Kentucky, United States of America
PLoS Negl Trop Dis 8:e2728. 2014..We discuss our findings in light of the evolution of Wolbachia infections in the tsetse fly and their potential impacts on the control of tsetse populations and trypanosomiasis. ..
- Trypanosoma brucei gambiense group 1 is distinguished by a unique amino acid substitution in the HpHb receptor implicated in human serum resistanceRebecca E Symula
Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut, United States of America
PLoS Negl Trop Dis 6:e1728. 2012..In contrast, similarity in HpHbR sequence among isolates of Tbg group 2 and Tbb/Tbr provides further evidence that human serum resistance in Tbg group 2 is likely independent of HpHbR function...
- Tsetse-Wolbachia symbiosis: comes of age and has great potential for pest and disease controlVangelis Doudoumis
Department of Environmental and Natural Resources Management, University of Ioannina, 2 Seferi St, 30100 Agrinio, Greece
J Invertebr Pathol 112:S94-103. 2013....
- Improving Sterile Insect Technique (SIT) for tsetse flies through research on their symbionts and pathogensAdly M M Abd-Alla
Insect Pest Control Laboratory, Joint FAO IAEA Division of Nuclear Techniques in Food and Agriculture, Vienna, Austria
J Invertebr Pathol 112:S2-10. 2013..The results of the CRP and the solutions envisaged to alleviate the constraints of the mass rearing of tsetse flies for SIT are presented in this special issue...
- Intercommunity effects on microbiome and GpSGHV density regulation in tsetse fliesJingwen Wang
Division of Epidemiology of Microbial Disease, Yale School of Public Health, Yale University, New Haven, CT, USA
J Invertebr Pathol 112:S32-9. 2013..Our findings suggest that in addition to the host immune system, interdependencies between symbiotic partners result in a highly tuned density regulation for tsetse's microbiome...
- The population structure of Glossina fuscipes fuscipes in the Lake Victoria basin in Uganda: implications for vector controlChaz Hyseni
Department of Ecology and Evolutionary Biology, Yale University, 21 Sachem Street, New Haven, CT, USA
Parasit Vectors 5:222. 2012..We screened tsetse flies from the three Ugandan PATTEC blocks for genetic diversity at 15 microsatellite loci from continental and offshore populations to provide empirical data to support this initiative...
- Permanent genetic resources added to molecular ecology resources database 1 October 2012-30 November 2012Serap Aksoy
Molecular Ecology Resources Editorial Office, 6270 University Blvd, Vancouver, BC, V6T 1Z4, Canada
Mol Ecol Resour 13:341-3. 2013....
- Phylogeography and population structure of Glossina fuscipes fuscipes in Uganda: implications for control of tsetseJon S Beadell
Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut, United States of America
PLoS Negl Trop Dis 4:e636. 2010..Population genetics can help to resolve this issue by characterizing the extent of linkage among apparently isolated groups of tsetse...
- Wolbachia association with the tsetse fly, Glossina fuscipes fuscipes, reveals high levels of genetic diversity and complex evolutionary dynamicsRebecca E Symula
Department of Ecology and Evolutionary Biology, Yale University, 21 Sachem St, New Haven, CT, USA
BMC Evol Biol 13:31. 2013....
- High levels of genetic differentiation between Ugandan Glossina fuscipes fuscipes populations separated by Lake KyogaPatrick P Abila
National Livestock Resources Research Institute, Tororo, Uganda
PLoS Negl Trop Dis 2:e242. 2008..gambiense. Uganda is exceptional in that it harbors both parasites, which are separated by a narrow 160-km belt. This separation is puzzling considering there are no restrictions on the movement of people and animals across this region...
- Glossina fuscipes populations provide insights for human African trypanosomiasis transmission in UgandaSerap Aksoy
Yale School of Public Health, Department of Epidemiology of Microbial Diseases, Yale University, 60 College Street, New Haven, CT, USA
Trends Parasitol 29:394-406. 2013..We discuss the implications of these findings for large-scale tsetse control programs, including suppression or eradication, being undertaken in Uganda, and potential future genetic applications. ..
- Evaluating paratransgenesis as a potential control strategy for African trypanosomiasisJan Medlock
Department of Biological Sciences, Oregon State University, Corvallis, Oregon, United States of America
PLoS Negl Trop Dis 7:e2374. 2013....
- Tissue distribution and transmission routes for the tsetse fly endosymbiontsSéverine Balmand
INSA Lyon, INRA, UMR203 BF2I, Biologie Fonctionnelle Insectes et Interactions, F 69621 Villeurbanne, France
J Invertebr Pathol 112:S116-22. 2013....
- Influence of host phylogeographic patterns and incomplete lineage sorting on within-species genetic variability in Wigglesworthia species, obligate symbionts of tsetse fliesRebecca E Symula
Department of Ecology and Evolutionary Biology, Yale University, 21 Sachem St, New Haven, CT 06520, USA
Appl Environ Microbiol 77:8400-8. 2011..Thus, understanding the adaptive value of these host-symbiont combinations may afford opportunities to develop vector control methods...
- Modeling transmission dynamics and control of vector-borne neglected tropical diseasesPaula M Luz
School of Public Health, Yale University, New Haven, Connecticut, USA
PLoS Negl Trop Dis 4:e761. 2010....
- A global sensitivity analysis for African sleeping sicknessStephen Davis
Yale School of Public Health, 60 College Street, P O Box 208034, New Haven, CT 06520, USA
Parasitology 138:516-26. 2011....
- Temporal stability of Glossina fuscipes fuscipes populations in UgandaRichard Echodu
Faculty of Science, Gulu University, Uganda
Parasit Vectors 4:19. 2011..f. fuscipes distributed across southeastern Uganda, including a zone of contact between two historically isolated lineages. A total of 667 tsetse flies were genotyped at 16 microsatellite loci and at one mitochondrial locus...
- Phylogeography and taxonomy of Trypanosoma bruceiOliver Balmer
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
PLoS Negl Trop Dis 5:e961. 2011..Characterizing the evolutionary relationships and population structure of parasites can provide important insights into the epidemiology of human disease...
- Polyandry is a common event in wild populations of the Tsetse fly Glossina fuscipes fuscipes and may impact population reduction measuresAngelica Bonomi
Department of Animal Biology, University of Pavia, Pavia, Italy
PLoS Negl Trop Dis 5:e1190. 2011..f. fuscipes has not been investigated in the laboratory or in the wild. Interest in assessing the presence of remating in Ugandan populations is driven by the fact that eradication of this species is at the planning stage in this country...
- Genetic diversity and population structure of Glossina pallidipes in Uganda and western KenyaJohnson O Ouma
Trypanosomiasis Research Centre, Kenya Agricultural Research Institute, Kikuyu, Kenya
Parasit Vectors 4:122. 2011..It is unknown whether the G. pallidipes belt in southeastern Uganda extends into western Kenya. We investigated the genetic diversity and population structure of G. pallidipes in Uganda and western Kenya...
- Multiple-strain infections of Trypanosoma brucei across AfricaOliver Balmer
Department of Ecology and Evolutionary Biology, Yale University, 165 Prospect Street, New Haven, CT 06511, USA
Acta Trop 107:275-9. 2008..Together with previous results, these findings strongly suggest that multiple-strain infections are common for this parasite and that their consequences for epidemiology and parasite evolution should be investigated in detail...
- Characterization of the antimicrobial peptide attacin loci from Glossina morsitansJ Wang
Yale University School of Medicine, Department of Epidemiology and Public Health, 60 College Street, New Haven, CT 06510, USA
Insect Mol Biol 17:293-302. 2008..Transcription of AttD is significantly less relative to the other two genes, and is preferentially induced in the fat body of parasitized flies. These results indicate that the different attacin genes may be differentially regulated...
- Infections with immunogenic trypanosomes reduce tsetse reproductive fitness: potential impact of different parasite strains on vector population structureChangyun Hu
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut, USA
PLoS Negl Trop Dis 2:e192. 2008..Potential repercussions for vector population growth, parasite-host coevolution, and disease prevalence are discussed...
- Prevention of nosocomial transmission of extensively drug-resistant tuberculosis in rural South African district hospitals: an epidemiological modelling studySanjay Basu
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA
Lancet 370:1500-7. 2007..We modelled the plausible effect of rapidly available infection control strategies on the overall course of the XDR tuberculosis epidemic in a rural area of South Africa...