Molecular Aspects of Tsetse and Trypanosome Transmission

Summary

Principal Investigator: S Aksoy
Affiliation: Yale University
Country: USA
Abstract: African trypanosomiasis is once again a major public health problem throughout much of Africa. Control strategies are limited due to the lack of mammalian vaccines and efficacious and affordable drugs. The recent developments in recombinant DNA technologies stand to improve existing vector control measures, but progress in this are has been hampered by the lack of information on the molecular aspects of tsetse and its interactions with trypanosomes. Tsetse flies are in general refractory to the transmission of African trypanosomes although the molecular basis for refractoriness is unknown. Pdor induction of the tsetse immune system can reduce parasite transmission indicating that tsetse's innate defense surveillance system is capable of terminating the development of trypanosomes. In the work proposed here, a comprehensive panel of immune-responsive genes will be identified using several different molecular strategies and their expression profiles in response to different immune challenges will be analyzed. Both systemic and local responses, respectively mediated by fat body and proventriculus tissue, will be investigated at the molecular level. Functional studies are proposed with several key antimicrobial gene products to understand their role in parasite transmission. This study will allow us to begin to understand the components of the tsetse immune system and the interactions they exhibit with trypanosomes during the parasite establishment and transmission in the fly. Although germ line transformation approach is difficult in tsetse because of its unusual reproductive biology, expression of transgenes in the gut symbionts of tsetse, particularly Sodalis glossinidius, may prove a valuable strategy to control disease transmission. Central to such a strategy will be identification of suitable genes for use as transgenes. Immunity genes are strong =candidates which this study may help to identify. These genes may also play a role in differentiation of trypanosomes and again, this project will identify potential candidates.
Funding Period: 2002-12-15 - 2008-11-30
more information: NIH RePORT

Top Publications

  1. pmc Insights into the trypanosome-host interactions revealed through transcriptomic analysis of parasitized tsetse fly salivary glands
    Erich Loza Telleria
    Yale School of Public Health, Department of Epidemiology of Microbial Diseases, LEPH, New Haven, Connecticut, United States of America
    PLoS Negl Trop Dis 8:e2649. 2014
  2. pmc Tissue distribution and transmission routes for the tsetse fly endosymbionts
    Séverine Balmand
    INSA Lyon, INRA, UMR203 BF2I, Biologie Fonctionnelle Insectes et Interactions, F 69621 Villeurbanne, France
    J Invertebr Pathol 112:S116-22. 2013
  3. pmc PGRP-LB is a maternally transmitted immune milk protein that influences symbiosis and parasitism in tsetse's offspring
    Jingwen Wang
    Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 109:10552-7. 2012
  4. pmc Tsetse-Wolbachia symbiosis: comes of age and has great potential for pest and disease control
    Vangelis Doudoumis
    Department of Environmental and Natural Resources Management, University of Ioannina, 2 Seferi St, 30100 Agrinio, Greece
    J Invertebr Pathol 112:S94-103. 2013
  5. doi Improving Sterile Insect Technique (SIT) for tsetse flies through research on their symbionts and pathogens
    Adly 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
  6. pmc Intercommunity effects on microbiome and GpSGHV density regulation in tsetse flies
    Jingwen 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
  7. pmc OmpA-mediated biofilm formation is essential for the commensal bacterium Sodalis glossinidius to colonize the tsetse fly gut
    Michele A Maltz
    Yale School of Public Health, Department of Epidemiology of Microbial Diseases, New Haven, Connecticut, USA
    Appl Environ Microbiol 78:7760-8. 2012
  8. pmc Characterization of the achromobactin iron acquisition operon in Sodalis glossinidius
    Caitlin L Smith
    Department of Biology, University of Richmond, Richmond, Virginia, USA
    Appl Environ Microbiol 79:2872-81. 2013
  9. pmc Tsetse fly microbiota: form and function
    Jingwen Wang
    Department of Epidemiology of Microbial Diseases, Yale School of Public Health New Haven, CT, USA
    Front Cell Infect Microbiol 3:69. 2013
  10. pmc Obligate symbionts activate immune system development in the tsetse fly
    Brian L Weiss
    Division of Epidemiology of Microbial Diseases, Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA
    J Immunol 188:3395-403. 2012

Scientific Experts

  • Brian L Weiss
  • Juliana Alves-Silva
  • S Aksoy
  • Dana Nayduch
  • Jingwen Wang
  • Geoffrey M Attardo
  • Yineng Wu
  • Nurper Guz
  • Adly M M Abd-Alla
  • Changyun Hu
  • Claudia Lohs
  • G M Attardo
  • Erich Loza Telleria
  • Corey Brelsfoard
  • Caitlin L Smith
  • Vangelis Doudoumis
  • Michelle O'Neill
  • Kostas Bourtzis
  • Séverine Balmand
  • Michele A Maltz
  • Amy F Savage
  • Abdelaziz Heddi
  • G Yang
  • J Wang
  • Roshan Pais
  • Patricia M Strickler-Dinglasan
  • Youjia Hu
  • Xin Zhao
  • Sandesh Regmi
  • Thiago Luiz Alves E Silva
  • Joshua B Benoit
  • Andrew G Parker
  • Uzma Alam
  • Drion G Boucias
  • George Tsiamis
  • Just M Vlak
  • Max Bergoin
  • Emre Aksoy
  • Laura J Runyen-Janecky
  • Nguya K Maniania
  • Jose Mc Ribeiro
  • C Lohs
  • Matthew Berriman
  • Suleyman Yildirim
  • M Hattori
  • Uzma H Alam
  • Rita V M Rio
  • Alison P Galvani
  • Terry W Pearson
  • A Toyoda
  • Lee R Haines
  • C Amemiya
  • C Hu
  • Y Wu
  • M Berriman
  • A Stuart
  • Jan Medlock
  • E Caler
  • S A H Perkin
  • P Strickler-Dinglasan
  • Geoffrey Attardo
  • M B Soares
  • N El-Sayeed
  • M F Bonaldo
  • Patricia Strickler-Dinglasan

Detail Information

Publications30

  1. pmc Insights into the trypanosome-host interactions revealed through transcriptomic analysis of parasitized tsetse fly salivary glands
    Erich Loza Telleria
    Yale School of Public Health, Department of Epidemiology of Microbial Diseases, LEPH, New Haven, Connecticut, United States of America
    PLoS Negl Trop Dis 8:e2649. 2014
    ..This study provides a foundation on the molecular aspects of the trypanosome dialogue with its tsetse and mammalian hosts, necessary for future functional investigations. ..
  2. pmc Tissue distribution and transmission routes for the tsetse fly endosymbionts
    Séverine Balmand
    INSA Lyon, INRA, UMR203 BF2I, Biologie Fonctionnelle Insectes et Interactions, F 69621 Villeurbanne, France
    J Invertebr Pathol 112:S116-22. 2013
    ....
  3. pmc PGRP-LB is a maternally transmitted immune milk protein that influences symbiosis and parasitism in tsetse's offspring
    Jingwen Wang
    Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 109:10552-7. 2012
    ..Thus, PGRP-LB plays a pivotal role in tsetse's fitness by protecting symbiosis against host-inflicted damage during development and by controlling parasite infections in adults that can otherwise reduce host fecundity...
  4. pmc Tsetse-Wolbachia symbiosis: comes of age and has great potential for pest and disease control
    Vangelis Doudoumis
    Department of Environmental and Natural Resources Management, University of Ioannina, 2 Seferi St, 30100 Agrinio, Greece
    J Invertebr Pathol 112:S94-103. 2013
    ....
  5. doi Improving Sterile Insect Technique (SIT) for tsetse flies through research on their symbionts and pathogens
    Adly 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...
  6. pmc Intercommunity effects on microbiome and GpSGHV density regulation in tsetse flies
    Jingwen 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...
  7. pmc OmpA-mediated biofilm formation is essential for the commensal bacterium Sodalis glossinidius to colonize the tsetse fly gut
    Michele A Maltz
    Yale School of Public Health, Department of Epidemiology of Microbial Diseases, New Haven, Connecticut, USA
    Appl Environ Microbiol 78:7760-8. 2012
    ..Acquiring a better understanding of the dynamics that promote Sodalis colonization of the tsetse gut may enhance the development of novel disease control strategies...
  8. pmc Characterization of the achromobactin iron acquisition operon in Sodalis glossinidius
    Caitlin L Smith
    Department of Biology, University of Richmond, Richmond, Virginia, USA
    Appl Environ Microbiol 79:2872-81. 2013
    ..Our findings suggest that Sodalis siderophores play a role in iron acquisition in certain tsetse fly tissues and provide evidence for the regulation of iron acquisition mechanisms in insect symbionts...
  9. pmc Tsetse fly microbiota: form and function
    Jingwen Wang
    Department of Epidemiology of Microbial Diseases, Yale School of Public Health New Haven, CT, USA
    Front Cell Infect Microbiol 3:69. 2013
    ..This review provides a detailed description of tsetse's microbiome, and describes the physiology underlying host-microbe, and microbe-microbe, interactions that occur in this fly. ..
  10. pmc Obligate symbionts activate immune system development in the tsetse fly
    Brian L Weiss
    Division of Epidemiology of Microbial Diseases, Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA
    J Immunol 188:3395-403. 2012
    ..Our finding that molecular components of Wigglesworthia exhibit immunostimulatory activity within tsetse is representative of a novel evolutionary adaptation that steadfastly links an obligate symbiont with its host...
  11. pmc Microbiome influences on insect host vector competence
    Brian Weiss
    Department of Epidemiology and Public Health, Yale School of Public Health, New Haven, CT 06520, USA
    Trends Parasitol 27:514-22. 2011
    ....
  12. pmc Tsetse immune system maturation requires the presence of obligate symbionts in larvae
    Brian L Weiss
    Department of Epidemiology and Public Health, Division of Epidemiology of Microbial Diseases, Yale University School of Medicine, New Haven, Connecticut, United States of America
    PLoS Biol 9:e1000619. 2011
    ..This phenomenon provides evidence of yet another important physiological adaptation that further anchors the obligate symbiosis between tsetse and Wigglesworthia...
  13. pmc An insight into the sialome of Glossina morsitans morsitans
    Juliana Alves-Silva
    Vector Group, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
    BMC Genomics 11:213. 2010
    ..Adult tsetse flies feed exclusively on vertebrate blood and are important vectors of human and animal diseases. Thus far, only limited information exists regarding the Glossina sialome, or any other fly belonging to the Hippoboscidae...
  14. pmc Transcriptome analysis of reproductive tissue and intrauterine developmental stages of the tsetse fly (Glossina morsitans morsitans)
    Geoffrey M Attardo
    Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT, USA
    BMC Genomics 11:160. 2010
    ..3438 expressed sequence tags were sequenced and analyzed...
  15. pmc Molecular characterization of two novel milk proteins in the tsetse fly (Glossina morsitans morsitans)
    G Yang
    Yale School of Public Health, Division of Epidemiology of Microbial Diseases, New Haven, CT 06510, USA
    Insect Mol Biol 19:253-62. 2010
    ..To understand milk protein function and regulation during viviparous reproduction, milk proteins need to be identified and characterized...
  16. ncbi Interactions among multiple genomes: tsetse, its symbionts and trypanosomes
    Serap Aksoy
    Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College St, 606 LEPH, New Haven, CT 06510, USA
    Insect Biochem Mol Biol 35:691-8. 2005
    ....
  17. ncbi Innate immune responses regulate trypanosome parasite infection of the tsetse fly Glossina morsitans morsitans
    Changyun Hu
    Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College St, 606 LEPH, New Haven, CT 06510, USA
    Mol Microbiol 60:1194-204. 2006
    ..Our results provide the first direct evidence for the involvement of antimicrobial peptides in trypanosome transmission in tsetse...
  18. ncbi Analysis of fat body transcriptome from the adult tsetse fly, Glossina morsitans morsitans
    G M Attardo
    Department of Epidemiology and Public Health, Section of Vector Biology, Yale University School of Medicine, New Haven, CT 06510, USA
    Insect Mol Biol 15:411-24. 2006
    ..Milk gland protein, apparently important for larval nutrition, however, is primarily synthesized by accessory milk gland tissue...
  19. pmc Interspecific transfer of bacterial endosymbionts between tsetse fly species: infection establishment and effect on host fitness
    Brian L Weiss
    Department of Epidemiology and Public Health, Yale University School of Medicine, LEPH 606, 60 College Street, New Haven, CT 06510, USA
    Appl Environ Microbiol 72:7013-21. 2006
    ..Our ability to transinfect tsetse flies is indicative of Sodalis ' recent evolutionary history with its tsetse fly host and demonstrates that this procedure may be used as a means of streamlining future paratransgenesis experiments...
  20. pmc Molecular aspects of viviparous reproductive biology of the tsetse fly (Glossina morsitans morsitans): regulation of yolk and milk gland protein synthesis
    Geoffrey M Attardo
    Department of Epidemiology and Public Health, Yale University School of Medicine, 606 LEPH New Haven, CT 06510, USA
    J Insect Physiol 52:1128-36. 2006
    ..These results demonstrate that both GmmYP1 and GmmMGP are involved in tsetse reproductive biology, the former associated with the process of oogenesis and the latter with larvigenesis...
  21. pmc Molecular characterization of iron binding proteins from Glossina morsitans morsitans (Diptera: Glossinidae)
    Patricia M Strickler-Dinglasan
    Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06510, USA
    Insect Biochem Mol Biol 36:921-33. 2006
    ..On the other hand, GmmFer1HCH maintains both the conserved ferroxidase center and the 5'UTR IRE; however, transcript variants suggest a more extensive regulatory mechanism for this subunit...
  22. pmc Molecular aspects of transferrin expression in the tsetse fly (Glossina morsitans morsitans)
    Nurper Guz
    Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College Street, 606 LEPH, New Haven, CT 06510, USA
    J Insect Physiol 53:715-23. 2007
    ..Analysis of tsetse that have cured the parasite challenge shows normal levels of GmmTsf. This observation suggests that the parasite in competing for the availability of limited dietary iron may manipulate host gene expression...
  23. ncbi Refractoriness in tsetse flies (Diptera: Glossinidae) may be a matter of timing
    Dana Nayduch
    Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06510, USA
    J Med Entomol 44:660-5. 2007
    ..pallidipes. The role of early, uninduced attacin expression, and its role in relative refractoriness in tsetse, is discussed...
  24. pmc Infections with immunogenic trypanosomes reduce tsetse reproductive fitness: potential impact of different parasite strains on vector population structure
    Changyun 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...
  25. pmc Characterization of the antimicrobial peptide attacin loci from Glossina morsitans
    J 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...
  26. pmc Analysis of milk gland structure and function in Glossina morsitans: milk protein production, symbiont populations and fecundity
    Geoffrey M Attardo
    Yale School of Public Health, Department of Epidemiology and Microbial Diseases, 60 College Street, 606 LEPH New Haven, CT 06510, USA
    J Insect Physiol 54:1236-42. 2008
    ..We discuss the significance of the milk gland in larval nutrition and in transmission of symbiotic bacteria to developing offspring...
  27. pmc The obligate mutualist Wigglesworthia glossinidia influences reproduction, digestion, and immunity processes of its host, the tsetse fly
    Roshan Pais
    Yale School of Public Heath, Department of Epidemiology of Microbial Diseases, New Haven, CT 06520, USA
    Appl Environ Microbiol 74:5965-74. 2008
    ..The ability to rear adult tsetse that lack the obligate Wigglesworthia endosymbionts will now enable functional investigations into this ancient symbiosis...
  28. pmc An insect symbiosis is influenced by bacterium-specific polymorphisms in outer-membrane protein A
    Brian L Weiss
    Department of Epidemiology and Public Health, Section of Vector Biology, Yale University School of Medicine, LEPH 606, 60 College Street, New Haven, CT 06520, USA
    Proc Natl Acad Sci U S A 105:15088-93. 2008
    ..coli K12. Our results show that polymorphisms in the exposed loop domains of OmpA represent a microbial adaptation that mediates host tolerance of endogenous symbiotic bacteria...
  29. ncbi An antimicrobial peptide with trypanocidal activity characterized from Glossina morsitans morsitans
    Youjia Hu
    Department of Epidemiology and Public Health, Section of Vector Biology, Yale University, School of Medicine, 60 College St, 606 LEPH, New Haven, CT 06510, USA
    Insect Biochem Mol Biol 35:105-15. 2005
    ..We discuss a paratransgenic strategy, which involves the expression of trypanocidal molecules such as recGmAttA1 in the midgut symbiont Sodalis in vivo to reduce trypanosome transmission...