Skip to main content Accessibility help
×
Home

The mitochondrial heat shock protein 60 (HSP60) is up-regulated in Onchocerca volvulus after the depletion of Wolbachia

  • K. M. PFARR (a1), U. HEIDER (a1), C. SCHMETZ (a2), D. W. BÜTTNER (a2) and A. HOERAUF (a1)...

Summary

Wolbachia, a genus of endosymbiotic bacteria of filarial worms, represent novel targets for anti-filarial therapy. The efficacy of compounds against Wolbachia has been evaluated using antiserum raised against the 60 kDa heat shock protein (HSP60) which binds specifically to this protein in both Wolbachia and mitochondria. It has been shown that Wolbachia stains (using such specific probes) stronger than the mitochondria in untreated Onchocerca volvulus, whereas after the depletion of Wolbachia (with drugs) staining of the mitochondria is increased. Herein, immunogold electron microscopy showed that specific anti-HSP60 serum specifically labelled Wolbachia and filarial mitochondria, and that both have distinct localization patterns, thus allowing them to be differentiated. Immunohistochemistry of O. volvulus showed that HSP60 staining is increased in the mitochondria after Wolbachia depletion in the hypodermis, epithelia, muscles, oocytes, embryos, and developing spermatozoa. This could have been the result of the antiserum preferentially binding to the Wolbachia when they are present or due to increased expression of the protein in the absence of the bacteria. To address this, mRNA levels of filarial hsp60 in O. volvulus were measured. After the depletion of Wolbachia, the transcription of hsp60 was significantly greater (7·7 fold) compared with untreated worms. We hypothesize that the increased expression of HSP60 in the absence of Wolbachia is due to a disruption of the homeostasis of the endosymbiosis.

Copyright

Corresponding author

*Corresponding author: Institute for Medical Parasitology, University of Bonn, Sigmund-Freud-Strasse 25, D-53105, Bonn, Germany. Tel: +49 228 287 11510. Fax: +49 228 287 14330. E-mail: pfarr@parasit.meb.uni-bonn.de

References

Hide All
Bandi, C., Anderson, T. J. C., Genchi, C. and Blaxter, M. L. (1998). Phylogeny of Wolbachia in filarial nematodes. Proceedings of the Royal Society of London, B 265, 24072413.
Basañez, M. G., Pion, S. D., Churcher, T. S., Breitling, L., Little, M. P. and Boussinesq, M. (2006). River Blindness: A success story under threat? PLoS Medicine 3.
Brattig, N. W., Bazzocchi, C., Kirschning, C. J., Reiling, N., Büttner, D. W., Ceciliani, F., Geisinger, F., Hochrein, H., Ernst, M., Wagner, H., Bandi, C. and Hoerauf, A. (2004). The major surface protein of Wolbachia endosymbionts in filarial nematodes elicits responses through TLR2 and TLR4. Journal of Immunology 173, 437445.
Büttner, D. W., Wanji, S., Bazzocchi, C., Bain, O. and Fischer, P. (2003). Obligatory symbiotic Wolbachia endobacteria are absent from Loa loa. Filaria Journal 2, 10.
Duke, B. O., Marty, A. M., Peett, D. L., Gardo, J., Pion, S. D., Kamgno, J. and Boussinesq, M. (2002). Neoplastic change in Onchocerca volvulus and its relation to ivermectin treatment. Parasitology 125, 431444.
Foster, J., Ganatra, M., Kamal, I., Ware, J., Makarova, K., Ivanova, N., Bhattacharyya, A., Kapatral, V., Kumar, S., Posfai, J., Vincze, T., Ingram, J., Moran, L., Lapidus, A., Omelchenko, M., Kyripide, N., Ghedin, E., Wang, S., Goltsman, E., Joukov, V., Ostravskaya, O., Tsukerman, K., Mazur, M., Comb, D., Koonin, E. and Slatko, B. (2005). The Wolbachia genome of Brugia malayi: endosymbiont evolution within a human pathogenic nematode. PLoS Biology 3, e121.
Franz, M. (1988). The morphology of adult Onchocerca volvulus based on electron microscopy. Tropical Medicine and Parasitology 39 (Suppl. 4), 359366.
Franz, M. and Büttner, D. W. (1983). The fine structure of adult Onchocerca volvulus IV. The hypodermal chords of the female worm. Tropenmedizin und Parasitologie 34, 122128.
Gilbert, J., Nfon, C. K., Makepeace, B. L., Njongmeta, L. M., Hastings, I. M., Pfarr, K. M., Renz, A., Tanya, V. N. and Trees, A. J. (2005). Antibiotic chemotherapy of onchocerciasis: in a bovine model, killing of adult parasites requires a sustained depletion of endosymbiotic bacteria (Wolbachia species). Journal of Infectious Diseases 192, 14831493.
Heider, U., Blaxter, M., Hoerauf, A. and Pfarr, K. M. (2006). Differential display of genes expressed in the filarial nematode Litomosoides sigmodontis reveals a putative phosphate permease up-regulated after depletion of Wolbachia endobacteria. International Journal of Medical Microbiology 296, 287299.
Hoerauf, A. (2000). Intrazelluläre Bakterien der Gattung Wolbachia in Würmern – Ziel therapeutischer Intervention? Nova Acta Leopoldina 316, 262274.
Hoerauf, A. (2006). New strategies to combat filariasis. Expert Reviews of Anti-Infective Therapy 4, 211222.
Hoerauf, A., Mand, S., Volkmann, L., Büttner, M., Marfo-Debrekyei, Y., Taylor, M., Adjei, O. and Büttner, D. W. (2003). Doxycycline in the treatment of human onchocerciasis: Kinetics of Wolbachia endobacteria reduction and of inhibition of embryogenesis in female Onchocerca worms. Microbes and Infection 5, 261273.
Hoerauf, A., Nissen-Pähle, K., Schmetz, C., Henkle-Dührsen, K., Blaxter, M. L., Büttner, D. W., Gallin, M. Y., Al-Qaoud, K. M., Lucius, R. and Fleischer, B. (1999). Tetracycline therapy targets intracellular bacteria in the filarial nematode Litomosoides sigmodontis and results in filarial infertility. Journal of Clinical Investigation 103, 1118.
Hoerauf, A., Specht, S., Büttner, M., Pfarr, K., Mand, S., Fimmers, R., Marfo-Debrekyei, Y., Konadu, P., Debrah, A. Y., Bandi, C., Brattig, N., Albers, A., Larbi, J., Batsa, L., Adjei, O. and Büttner, D. W. (2007). Wolbachia endobacteria depletion by doxycycline as antifilarial therapy has macrofilaricidal activity in onchocerciasis: A randomized placebo-controlled study. Medical Microbiology and Immunology (Berlin) (in the Press). DOI: 10.1007/S00430-007-0062-1.
Kozek, W. J. and Figueroa Marroquin, H. (1977). Intracytoplasmic bacteria in Onchocerca volvulus. American Journal of Tropical Medicine and Hygiene 26, 663678.
Kramer, L. H., Passeri, B., Corona, S., Simoncini, L. and Casiraghi, M. (2003). Immunohistochemical/immunogold detection and distribution of the endosymbiont Wolbachia of Dirofilaria immitis and Brugia pahangi using a polyclonal antiserum raised against WSP (Wolbachia surface protein). Parasitology Research 89, 381386.
Molyneux, D. H., Bradley, M., Hoerauf, A., Kyelem, D. and Taylor, M. J. (2003). Mass drug treatment for lymphatic filariasis and onchocerciasis. Trends in Parasitology 19, 516522.
Pfarr, K. and Hoerauf, A. (2005). The annotated genome of Wolbachia from the filarial nematode Brugia malayi: what it means for progress in antifilarial medicine. PLoS Medicine 2, e110.
Plenge-Bönig, A., Kromer, M. and Büttner, D. W. (1995). Light and electron microscopy studies on Onchocerca jakutensis and O. flexuosa of red deer show different host-parasite interactions. Parasitology Research 81, 6673.
Taylor, M. J., Bandi, C. and Hoerauf, A. (2005 a). Wolbachia bacterial endosymbionts of filarial nematodes. Advances in Parasitology 60, 245284.
Taylor, M. J. and Hoerauf, A. (1999). Wolbachia bacteria of filarial nematodes. Parasitology Today 15, 437442.
Taylor, M. J., Makunde, W. H., Mcgarry, H. F., Turner, J. D., Mand, S. and Hoerauf, A. (2005 b). Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo-controlled trial. Lancet 365, 21162121.
WHO (2007). Meeting of the International Task Force for Disease Eradication – 11 January 2007. Weekly Epidemiological Record 82, 197202.
Wu, Y., Egerton, G., Ball, A., Tanguay, R. M. and Bianco, A. E. (2000). Characterization of the heat-shock protein 60 chaperonin from Onchocerca volvulus. Molecular and Biochemical Parasitology 107, 155168.
Yoneda, T., Benedetti, C., Urano, F., Clark, S. G., Harding, H. P. and Ron, D. (2004). Compartment-specific perturbation of protein handling activates genes encoding mitochondrial chaperones. Journal of Cell Science 117, 40554066.
Zhao, Q., Wang, J., Levichkin, I. V., Stasinopoulos, S., Ryan, M. T. and Hoogenraad, N. J. (2002). A mitochondrial specific stress response in mammalian cells. EMBO Journal 21, 44114419.

Keywords

Related content

Powered by UNSILO
Type Description Title
PDF
Supplementary materials

Pfarr supplementary material
Supplementary figure

 PDF (165 KB)
165 KB

The mitochondrial heat shock protein 60 (HSP60) is up-regulated in Onchocerca volvulus after the depletion of Wolbachia

  • K. M. PFARR (a1), U. HEIDER (a1), C. SCHMETZ (a2), D. W. BÜTTNER (a2) and A. HOERAUF (a1)...

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.