• 1.

    Balmer O, Caccone A, 2008. Multiple-strain infections of Trypanosoma brucei across Africa. Acta Trop 107: 275279.

  • 2.

    Warren RM, Victor TC, Streicher EM, Richardson M, Beyers N, Gey van Pittius NC, van Helden PD, 2004. Patients with active tuberculosis often have different strains in the same sputum specimen. Am J Respir Crit Care Med 169: 610614.

    • Search Google Scholar
    • Export Citation
  • 3.

    Sharp GB, Kawaoka Y, Jones DJ, Bean WJ, Pryor SP, Hinshaw V, Webster RG, 1997. Coinfection of wild ducks by influenza A viruses: distribution patterns and biological significance. J Virol 71: 61286135.

    • Search Google Scholar
    • Export Citation
  • 4.

    Schmid-Hempel P, Reber Funk C, 2004. The distribution of genotypes of the trypanosome parasite, Crithidia bombi, in populations of its host, Bombus terrestris. Parasitology 129: 147158.

    • Search Google Scholar
    • Export Citation
  • 5.

    Keeney DB, Waters JM, Poulin R, 2007. Clonal diversity of the marine trematode Maritrema novaezealandensis within intermediate hosts: the molecular ecology of parasite life cycles. Mol Ecol 16: 431439.

    • Search Google Scholar
    • Export Citation
  • 6.

    Balmer O, Stearns SC, Schötzau A, Brun R, 2009. Intraspecific competition between co-infecting parasite strains enhances host survival in African trypanosomes. Ecology 90: 33673378.

    • Search Google Scholar
    • Export Citation
  • 7.

    Smith T, Beck HP, Kitua A, Mwankusye S, Felger I, Fraser-Hurt N, Irion A, Alonso P, Teuscher T, Tanner M, 1999. Age dependence of the multiplicity of Plasmodium falciparum infections and of other malariological indices in an area of high endemicity. Trans R Soc Trop Med Hyg 93 (Suppl 1): 1520.

    • Search Google Scholar
    • Export Citation
  • 8.

    Van Wijngaerden E, Peetermans WE, Van Lierde S, Van Eldere J, 1997. Polyclonal Staphylococcus endocarditis. Clin Infect Dis 25: 6971.

  • 9.

    Rijnders BJ, Van Wijngaerden E, Van Eldere J, Peetermans WE, 2001. Polyclonal Staphylococcus epidermidis intravascular catheter-related infections. Clin Microbiol Infect 7: 388391.

    • Search Google Scholar
    • Export Citation
  • 10.

    Maudlin I, Holmes PH, Miles MA, 2004. The Trypanosomiases. Wallingford, UK: CABI Publishing.

  • 11.

    Mulligan HW, Potts WH, 1970. The African Trypanosomiases. New York: Wiley-Interscience.

  • 12.

    Barrett MP, Burchmore RJ, Stich A, Lazzari JO, Frasch AC, Cazzulo JJ, Krishna S, 2003. The trypanosomiases. Lancet 362: 14691480.

  • 13.

    Brun R, Balmer O, 2006. New developments in human African trypanosomiasis. Curr Opin Infect Dis 19: 415420.

  • 14.

    MacLean L, Odiit M, MacLeod A, Morrison L, Sweeney L, Cooper A, Kennedy PG, Sternberg JM, 2007. Spatially and genetically distinct African trypanosome virulence variants defined by host interferon-gamma response. J Infect Dis 196: 16201628.

    • Search Google Scholar
    • Export Citation
  • 15.

    Wang Y, Holmes E, Nicholson JK, Cloarec O, Chollet J, Tanner M, Singer BH, Utzinger J, 2004. Metabonomic investigations in mice infected with Schistosoma mansoni: an approach for biomarker identification. Proc Natl Acad Sci USA 101: 1267612681.

    • Search Google Scholar
    • Export Citation
  • 16.

    Lindon JC, Nicholson JK, Holmes E, Everett JR, 2000. Metabonomics: metabolic processes studied by NMR spectroscopy of biofluids. Concepts Magn Reson 12: 289320.

    • Search Google Scholar
    • Export Citation
  • 17.

    Trygg J, Holmes E, Lundstedt T, 2007. Chemometrics in metabonomics. J Proteome Res 6: 469479.

  • 18.

    Trygg J, Wold S, 2002. Orthogonal projections to latent structures (O-PLS). J Chemometr 16: 119128.

  • 19.

    Wang Y, Li JV, Saric J, Keiser J, Wu J, Utzinger J, Holmes E, 2010. Advances in metabolic profiling of experimental nematode and trematode infections. Adv Parasitol 73: 373404.

    • Search Google Scholar
    • Export Citation
  • 20.

    Pullan R, Brooker S, 2008. The health impact of polyparasitism in humans: are we under-estimating the burden of parasitic diseases? Parasitology 135: 783794.

    • Search Google Scholar
    • Export Citation
  • 21.

    Steinmann P, Utzinger J, Du ZW, Zhou XN, 2010. Multiparasitism a neglected reality on global, regional and local scale. Adv Parasitol 73: 2150.

  • 22.

    Wu JF, Holmes E, Xue J, Xiao SH, Singer BH, Tang HR, Utzinger J, Wang YL, 2010. Metabolic alterations in the hamster co-infected with Schistosoma japonicum and Necator americanus. Int J Parasitol 40: 695703.

    • Search Google Scholar
    • Export Citation
  • 23.

    Wang YL, Utzinger J, Saric J, Li JV, Burckhardt J, Dirnhofer S, Nicholson JK, Singer BH, Brun R, Holmes E, 2008. Global metabolic responses of mice to Trypanosoma brucei brucei infection. Proc Natl Acad Sci USA 105: 61276132.

    • Search Google Scholar
    • Export Citation
  • 24.

    Balmer O, Tostado C, 2006. New fluorescence markers to distinguish co-infecting Trypanosoma brucei strains in experimental multiple infections. Acta Trop 97: 94101.

    • Search Google Scholar
    • Export Citation
  • 25.

    Balmer O, Palma C, MacLeod A, Caccone A, 2006. Characterization of di-, tri- and tetranucleotide microsatellite markers with perfect repeats for Trypanosoma brucei and related species. Mol Ecol Notes 6: 508510.

    • Search Google Scholar
    • Export Citation
  • 26.

    R Development Core Team, 2005. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Development Core Team.

  • 27.

    Bylesjo M, Rantalainen M, Cloarec O, Nicholson JK, Holmes E, Trygg J, 2006. OPLS discriminant analysis: combining the strengths of PLS-DA and SIMCA classification. J Chemometr 20: 341351.

    • Search Google Scholar
    • Export Citation
  • 28.

    Li JV, Wang Y, Saric J, Nicholson JK, Dirnhofer S, Singer BH, Tanner M, Wittlin S, Holmes E, Utzinger J, 2008. Global metabolic responses of NMRI mice to an experimental Plasmodium berghei infection. J Proteome Res 7: 39483956.

    • Search Google Scholar
    • Export Citation
  • 29.

    Saric J, Li JV, Wang YL, Keiser J, Bundy JG, Holmes E, Utzinger J, 2008. Metabolic profiling of an Echinostoma caproni infection in the mouse for biomarker discovery. PLoS Negl Trop Dis 2: e254.

    • Search Google Scholar
    • Export Citation
  • 30.

    Abramowitz M, Stegun IA, 1964. Handbook of Mathematical Functions with Formulas, Graphs, and Mathematical Tables. Washington, DC: U.S. Government Printing Office, 1046.

    • Search Google Scholar
    • Export Citation
  • 31.

    Stibbs HH, Seed JR, 1975. Metabolism of tyrosine and phenylalanine in Trypanosoma brucei gambiense. Int J Biochem 6: 197203.

  • 32.

    El Sawalhy A, Seed JR, Hall JE, El Attar H, 1998. Increased excretion of aromatic amino acid catabolites in animals infected with Trypanosoma brucei evansi. J Parasitol 84: 469473.

    • Search Google Scholar
    • Export Citation
  • 33.

    Cazzulo JJ, 1992. Aerobic fermentation of glucose by trypanosomatids. FASEB J 6: 31533161.

  • 34.

    Bakker BM, Michels PA, Opperdoes FR, Westerhoff HV, 1999. What controls glycolysis in bloodstream form Trypanosoma brucei? J Biol Chem 274: 1455114559.

    • Search Google Scholar
    • Export Citation
  • 35.

    Sant'Ana CD, Menaldo DL, Costa TR, Godoy H, Muller VD, Aquino VH, Albuquerque S, Sampaio SV, Monteiro MC, Stábeli RG, Soares AM, 2008. Antiviral and antiparasite properties of an L-amino acid oxidase from the snake Bothrops jararaca: cloning and identification of a complete cDNA sequence. Biochem Pharmacol 76: 279288.

    • Search Google Scholar
    • Export Citation
  • 36.

    Franca SC, Kashima S, Roberto PG, Marins M, Ticli FK, Pereira JO, Astolfi-Filho S, Stábeli RG, Magro AJ, Fontes MR, Sampaio SV, Soares AM, 2007. Molecular approaches for structural characterization of Bothrops L-amino acid oxidases with antiprotozoal activity: cDNA cloning, comparative sequence analysis, and molecular modeling. Biochem Biophys Res Commun 355: 302306.

    • Search Google Scholar
    • Export Citation
  • 37.

    Chlopicki S, Swies J, Mogielnicki A, Buczko W, Bartus M, Lomnicka M, Adamus J, Gebicki J, 2007. 1-Methylnicotinamide (MNA), a primary metabolite of nicotinamide, exerts anti-thrombotic activity mediated by a cyclooxygenase-2/prostacyclin pathway. Br J Pharmacol 152: 230239.

    • Search Google Scholar
    • Export Citation

 

 

 

 

Metabonomic Investigation of Single and Multiple Strain Trypanosoma brucei brucei Infections

View More View Less
  • Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom; State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, People's Republic of China; Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland; Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland; Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut; Institute of Zoology, University of Basel, Basel, Switzerland

Although co-infections are common and can have important epidemiologic and evolutionary consequences, studies exploring biochemical effects of multiple-strain infections remain scarce. We studied metabolic responses of NMRI mice to Trypanosoma brucei brucei single (STIB777AE-Green1 or STIB246BA-Red1) and co-infections using a 1H nuclear magnetic resonance (NMR) spectroscopy-based metabolic profiling strategy. All T. b. brucei infections caused an alteration in urinary biochemical composition by day 4 postinfection, characterized by increased concentrations of 2-oxoisocaproate, D-3-hydroxybutyrate, lactate, 4-hydroxyphenylacetate, phenylpyruvate, and 4-hydroxyphenylpyruvate, and decreased levels of hippurate. Although there were no marked differences in metabolic signatures observed in the mouse infected with a single or dual strain of T. b. brucei, there was a slower metabolic response in mice infected with T. b. brucei green strain compared with mice infected with either the red strain or both strains concurrently. Pyruvate, phenylpyruvate, and hippurate were correlated with parasitemia, which might be useful in monitoring responses to therapeutic interventions.

Author Notes

*Address correspondence to Oliver Balmer, Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland. E-mail: oliver.balmer@aya.yale.edu

Financial support: This study received financial support from the Swiss National Science Foundation (JVL, JS, and JU, project no. PPOOB-102883 and PPOOB-119129), the Deputy Rector's Award at Imperial College London and Technologie Servier (JVL), the Wellcome Trust/Imperial College VIP award (JS, grant no. PS1041), the Sir Henry Wellcome Fellowship (JS, Wellcome Trust award no. P23665), the Chinese Academy of Sciences (YW, grant KJXC2-YW-W11), the U.S. National Science Foundation (OB, grant DEB-0408083), the Yale Institute of Biospheric Studies (OB), the Novartis Stiftung für medizinisch-biologische Forschung (OB), and the University of Basel Fonds zur Förderung des akademischen Nachwuchses (OB).

Authors' addresses: Jia V. Li, Jasmina Saric, and Elaine Holmes, Biomolecular Medicine, Department of Surgery and Cancer, Sir Alexander Fleming Building, Imperial College London, South Kensington, London, UK, E-mails: jia.li105@imperial.ac.uk, jasmina.saric@imperial.ac.uk, and elaine.holmes@imperial.ac.uk. Yulan Wang, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, People's Republic of China, E-mail: yulan.wang@wipm.ac.cn. Jürg Utzinger, Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel and University of Basel, Basel, Switzerland, E-mail: juerg.utzinger@unibas.ch. Oliver Balmer, Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Institute of Zoology, University of Basel, Basel, Switzerland and Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT, E-mail: oliver.balmer@aya.yale.edu.

Save