Skip to main content
SpringerLink
Log in

Chemotherapy of microsporidiosis: Benzimidazoles, fumagillin and polyamine analogues

  • Chapter
Opportunistic Infections: Toxoplasma, Sarcocystis, and Microsporidia

Part of the book series: World Class Parasites ((WCPA,volume 9))

Abstract

Microsporidia infection in humans is becoming increasingly recognized as a problem in immunocompromised as well as immune competent hosts. Human micropsoridian infections have been caused by several different microsporidian genera encompassing at least 12 species. Currently there are few controlled trials of the treatment of microsporidiosis in humans. Albendazole has been widely used for the treatment of microsporidiosis, however, it is clear from case reports that not all microsporidia are sensitive to this agent. Fumagillin has emerged as an alternative to albendazole treatment. This chapter discusses the recently identified enzyme target of fumagillin as well as the use of fumagilin in the treatment of microsporidiosis. Studies on polyamine metabolism of Encephalitozoon cuniculi indicate this organism relies primarily on uptake and interconversion of spermine to satisfy its polyamine requirements. Polyamine analogues having a bis aryl-3-7-3 configuration as well as pentamine and oligoamine analogues interfere with polyamine metabolism and cure model infections. These data suggest that the polyamine pathway should be a useful therapeutic target for the treatment of microsporidiosis. Polyamine metabolism in Enc. cuniculi is presented and discussed along with studies on the use of polyamine analogues in experimental models of infection.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Aarons, E. J., D. Woodrow, W. S. Hollister, E. U. Canning, Francis, and B. G. Gazzard. 1994. Reversible renal failure caused by a microsporidial infection. AIDS 8: 1119–1121.

    PubMed  CAS  Google Scholar 

  • Albrecht, H., I. Sobottka, H.J. Stellbrink, and H. Greten. 1995. Does the choice of Pneumocystis carinii prophylaxis influence the prevalence of Enterocytozoon bieneusi microsporidiosis in AIDS patients? [letter]. AIDS. 9: 302–3.

    PubMed  CAS  Google Scholar 

  • Anwar-Bruni, D.M., S.E. Hogan, D.A. Schwartz, C.M. Wilcox, R.T. Bryan, and J.L. Lennox. 1996. Atovaquone is effective treatment for the symptoms of gastrointestinal microsporidiosis in HIV-1-infected patients. AIDS 10: 619–23.

    PubMed  CAS  Google Scholar 

  • Armstrong, E. 1975. Fumidil B and benomyl: chemical control of Nosema king in Drosophila willistoni. Journal of Invertebrate Pathology 27: 363–366.

    Google Scholar 

  • Asmuth, D. M., P. C. DeGirolami, M. Federman, C.R. Ezratty, D.K. Pleskow, G. Desai and CA Wanke. 1994. Clinical features of microsporidiosis in AIDS. Clinical and Infectious Disease 18: 819–825.

    CAS  Google Scholar 

  • Azizul Haque, M., W. S. Hollister, A. Willcox, Canning E U. 1993. The antmicrosporidial activity of albendazole. Journal of Invertebrate Pathology 62: 171–177.

    Google Scholar 

  • Bacchi, C.J, H. C. Nathan, N. Yarlert, B. Goldberg, P. P. McCann, Am J. Bitonti, and A. Sjoerdsma. 1992. Cure of murine Trypanosma brucei rhodesiense infections with an S-adenyosylmethione decarboxylase inhibitor. Antimicrobial Agents Chemother 36: 2736–2740.

    CAS  Google Scholar 

  • —, J. Garofalo, M.A. Ciminelli, D. Rattendi, B. Goldberg, P.P. McCann, and N. Yarlett. 1993. Resistance to DL-α-difloromethylorntihine by clinical isolates of Typansoma brucei rhodesiense: role of S-adenosylmethionine. Biochemical Pharmacology 46: 471–481.

    PubMed  CAS  Google Scholar 

  • —, B. Goldberg, J. Garofalo-Hannan, D. Rattendi, P. Lyte, and N. Yarlett. 1995. Fate of soluble methionine in African trypanosomes: effects of metabolic inhibitors. Biochemical Journal 309: 737–743.

    PubMed  CAS  Google Scholar 

  • —, —, L.M. Weiss, N. Yarlett, P. Takvorian, A. Cali, and M. Wittner. 2001a. Polyamine synthesis and interconversion by the Microsporidian Encephalitozoon cuniculi. Journal of Eukaryotic Microbiology 48: 374–381.

    PubMed  Google Scholar 

  • —, and P.P. McCann. 1987. Parasitic protozoa and polyamines. In: Inhibition of polyamine metabolism: biological significance and basis for new therapies. P.P. McCann, A.E. Pegg, and A. Sjoerdsma (eds.) pp. 317–344. Academic Press, Orlando, FL.

    Google Scholar 

  • —, D. Orozco, L.M. Weiss, B. Frydman, V. Valasinas, N. Yarlett, L.J. Marton, M. Wittner. 2001b. SL-11158, a synthetic oligoamine, inhibits polyamine metabolism of Encephalitozoon cuniculi. Journal of Eukaryotic Microbiology 48: 92S–94S.

    Google Scholar 

  • —, L.M. Weiss, S. Lane, B. Frydman, A. Valasinas, V. Reddy, J.S. Sun, L.J. Marton, I. Khan, M. Moretto, N. Yarlett, and M. Wittner. 2002. Novel Synthetic Polyamines are effective in the treatment of experimental microsporidiosis: an opportunistic AIDS-associated infection. Antimicrobial Agents and Chemotherapy 46: 55–61.

    Google Scholar 

  • —, and N. Yarlett. 1993. Effects of antagonists of polyamine metabolism on African trypanosomes. Acta Tropica 54: 225–236.

    Google Scholar 

  • Beauvais, B., C. Sarfati, S. Challier, and F. Derouin. 1994. In vitro model to assess effect of antimicrobial agents on Encephalitozoon cuniculi. Antimicrobial Agents and Chemotherapy 38: 2440–2448.

    PubMed  CAS  Google Scholar 

  • Bergeron, R.J., W.R. Wiemar, G. Luchetta, C.A. Sninsky, and J. Weigand. 1995. Metabolism and pharmacokinetics of N 1, N 11-diethylhomospermine. Drug Metabolism and Disposition 23: 1117–1125.

    PubMed  CAS  Google Scholar 

  • —, —, —, —, —, 1996. Metabolism and pharmacokinetics of N 1, N 14-diethylhomospermine. Drug Metabolism and Disposition 24: 334–343.

    Google Scholar 

  • Bey, P., F.N. Bolkenius, N. Seiler, and P. Casara. 1985. N-2,3 butadienyl-1,4-butanediamine derivatives: potent irreversible inactivators of mammalian polyamine oxidase. Journal of Medicinal Chemistry 28: 1–2.

    PubMed  CAS  Google Scholar 

  • Blanshard, C, D. S. Ellis, S. P. Dowell, G. Towey, and B.G. Gazzard. 1993. Electron microscopic changes in Enterocytozoon bieneusi following treatment with albendazole. Journal of Clinical Pathology 46: 898–902.

    PubMed  CAS  Google Scholar 

  • —, —, D.G. Tovey, S. Dowell, and B.G. Gazzard. 1992. Treatment of intestinal microsporidiosis with albendazole in patients with AIDS. AIDS 6: 311–313.

    PubMed  Google Scholar 

  • Bitonti, A.J., J.A. Dumont, T.L. Bush, D.M. Stemerick, M.L. Edwards, and P.P. McCann. 1990. Bis(benzyl) polyamine analogs as novel substrates for polyamine oxidase. Journal of Biological Chemistry 265: 382–388.

    PubMed  CAS  Google Scholar 

  • Cali, A, D. P. Kotler, and J. M. Orenstein. 1993. Septata intestinalis N.G., N. Sp., an intestinal Microsporidian associated with chronic diarrhea and dissemination in AIDS patients. Journal of Eukaryotic Microbiology 40: 101–112.

    PubMed  CAS  Google Scholar 

  • —, P. M. Takvorian, S. Lewin, M. Rendel, C Sian, M. Wittner, and L. M. Weiss. 1996. Identification of a new nosema-like microsporidian associated with myositis in an AIDS patient. Journal of Eukaryotic Microbiology 43: 108S.

    PubMed  CAS  Google Scholar 

  • —, —, —, —, 1998. Brachiola vesicularum, N.G., N.Sp., a new microsporidium associated with AIDS and myositis. Journal of Eukaryotic Microbiology 45: 240–251.

    Google Scholar 

  • Casero, R.A., and A.E. Pegg. 1993. Spermidine/spermine N 1-acetyltransferase: the turning point in polyamine metabolism. FASEB Journal 7: 653–661.

    PubMed  CAS  Google Scholar 

  • —, and P.M. Woster. 2001. Terminally alkylated polyamine analogues as chemotherapeutic agents. Journal of Medicinal Chemistry 44: 1–26.

    PubMed  CAS  Google Scholar 

  • Chopp, G. L., J. Alroy, L. S. Adelman, J. C. Breen, and P. R. Skolnik. 1993. Myositis due to Pleistophora (Microsporidia) in a patient with AIDS. Clinical Infectious Disease 16: 15–21.

    Google Scholar 

  • Childs, R.E., and W.G. Bardsley. 1975. The steady state kinetics of peroxidase with 2,2′ azino-di-(3-ethyl-benzthiazoline-6-sulphonic acid) as chromogen. Biochemistry Journal 145: 93–103.

    CAS  Google Scholar 

  • Cohen, S. 1998. A guide to the polyamines. Oxford University Press, New York.

    Google Scholar 

  • Colbourn, N. I., W. S Hollister, A. Curry, and E. U. Canning. 1994. Activity of albendazole against Encephalitozoon cunicul in vitro. European Journal of Protistology 30: 211–220.

    Google Scholar 

  • Corcoran, G. D., J. R. Isaacson, C. Daniels, and P. L. Chiodini. 1996. Urethritis associated with disseminated microsporidiosis: clinical response to albendazole. Clinical Infectious Disease 22: 592–593.

    CAS  Google Scholar 

  • Costa, S., and L. Weiss. 2000. Drug treatment of microsporidiosis. Drug Resistance Updates 3: 1–16.

    Google Scholar 

  • Coyle. C., C. Bacchi, N. Yarlett, H.B. Tanowitz, M. Wittner, and L.M. Weiss. 1996. Polyamine Metabolism as a Therapeutic Target for Microsporidia. Journal of Eukaryotic Microbiology 43: 96S.

    PubMed  CAS  Google Scholar 

  • —, M. Kent, H. B. Tanowitz, M. Wittner, and L. M. Weiss. 1998. TNP-470 is an effective antimicrosporidial agent. Journal of Infectious Disease 177: 515–518.

    CAS  Google Scholar 

  • Danzin, C., P. Marchal, and P. Casara. 1990. Irreversible inhibition of rat S-adenosylmethionine decarboxylase by 5′{[(Z)-4-amino-2-butenyl]methylamino}-5′-deoxyadenosine. Biochemical Pharmacology 40: 1499–1503.

    PubMed  CAS  Google Scholar 

  • De Groote, M.A., G. Visvesvara, M.L. Wilson, N.J. Pieniazek, S.B. Slemenda, A.J. daSilva, G.J. Leitch, R.T. Bryan, and R. Reves. 1995. Polymerase chain reaction and culture confirmation of disseminated Encephalitozoon cuniculi in a patient with AIDS: successful therapy with albendazole. Journal of Infectious Disease 171: 1375–1378.

    Google Scholar 

  • Desportes, I., Y. Le Charpentier, A. Galian, F. Bernard, B. Cochand-Priollet B, A. Lavergne, P. Ravisse and R. Modigliani. 1985. Occurrence of a new microsporidian: Enterocytozoon bieneusi n.g., n.sp., in the enterocytes of a human patient with AIDS. Journal of Protozoology 32: 250–254.

    PubMed  CAS  Google Scholar 

  • Didier. E. S. 1997. Effects of albendazole, fumagillin, and TNP-470 on microsoridial replication in vitro. Antimicrobial Agents and Chemotherapy 41: 1541–1546.

    PubMed  CAS  Google Scholar 

  • —, J. A. Maddry, C. D. Kwong, L. C. Greeen, K. F. Snowden, and J. A. Shadduck. 1998. Screening of compounds for antimicrosporidial activity in vitro. Folia Parasitologica 45: 129–139.

    PubMed  Google Scholar 

  • —, P.W. Varner, P.J. Didier, A.M. Aldras, N.J. Millichamp, and M. Murphey-Corb. 1994. Experimental microsporidiosis in immuno-compotent and immuno-deficient mice and monkeys. Folia Parasitologica 41: 1–11.

    PubMed  Google Scholar 

  • Diesenhouse, M.C., L.A. Wilson, G.F. Corrent, G.S. Visvesvara, H.E. Grossniklaus, and R.T. Bryan. 1993. Treatment of microsporidial keratoconjunctivitis with topical fumagillin [see comments]. American Journal of Ophthalmology 115: 293–298.

    PubMed  CAS  Google Scholar 

  • Dieterich, D. T., E. A. Lew, D. P. Kotler, M. A. Poles, and J. M. Orenstien. 1994. Treatment with albendazole for intestinal disease due to Enterocytozoon bieneusi in patients with AIDS. Journal of Infectious Disease 169: 178–183.

    CAS  Google Scholar 

  • Dionisio, D., L. I. Manneschi, S. Di Lollo, A. Orsi, G. Sterrantino, M. Meli, M. Gabbrielli, A. Tani, A. Papucii, and F. Leoncini. 1997. Enterocytozoon bieneusi in AIDS: symptomatic relief and parasite changes after furazolidone. Journal of Clinical Pathology 50: 472–476.

    PubMed  CAS  Google Scholar 

  • Ditrich, O., Z. Kucerova, and B. Koudela, 1994. In vitro sensitivity of Encephalitozoon cuniculi and E. hellem to albendazole. Journal of Eukaryotic Microbiology 41: 37S.

    PubMed  CAS  Google Scholar 

  • Dore, G. J., D. J. Marriott, M. C. Hing, J. L. Harkness, and A. S. Field. 1995. Disseminated microsporidiosis due to Septata intestinalis in nine patients infected with the Human Immunodeficiency Virus: response to therapy with albendazole. Clinical Infectious Disease 21: 70–76.

    CAS  Google Scholar 

  • Edlind T, S. Katiyar, G. Visvesvara, and J. Li. 1996. Evolutionary origins of microsporidia and basis for benzimidazole sensitivity: an update. Journal of Eukaryotic Microbiology 43: 109S.

    PubMed  CAS  Google Scholar 

  • Edwards, M.L., N.J. Prakash, K.M. Stemerick, S.P. Sunkara, A.J. Bitonti, J.A. Dumont, P.P. McCann, P. Bey, and A. Sjoerdsma. 1990. Polyamine analogues with antitumor activity. Journal of Medicinal Chemistry 33: 1369–1375.

    PubMed  CAS  Google Scholar 

  • —, K.M. Stemetick, A.J. Bitonti, J.A. Dumont, P.P. McCann, P. Bey, and A. Sjoerdsma. 1991. Antimalarial polyamine analogs. Journal of Medicinal Chemistry 34: 567–574.

    Google Scholar 

  • Eeftinck Schattenkerk, J.K., T. van Gool, R.J. van Ketel, J.F. Bartelsman, C.L. Kuiken, W.J. Terpstra, and P. Reiss. 1991. Clinical significance of small-intestinal microsporidiosis in HIV-1-infected individuals [see comments]. Lancet 337: 895–898.

    PubMed  CAS  Google Scholar 

  • Fairlamb, A.H., and A. Cerami. 1992. Metabolism and functions of trypanothionine in the kinetoplastida. Annual Reviews in Microbiology 46: 695–729.

    CAS  Google Scholar 

  • —, G.B. Henderson, C.J. Bacchi, and A. Cerami. 1987. In vivo effects of difluoromethylornithine on trypanothione and polyamine levels in bloodstream forms of Trypanosoma brucei. Molecular and Biochemical Parasitology 24: 185–191.

    PubMed  CAS  Google Scholar 

  • Fayer R, and R. Fettere. 1995. Activity of benzimidazoles against cryptosporidiosis in neonatal BALB/c mice. Journal of Parasitology 81: 794–795.

    PubMed  CAS  Google Scholar 

  • Font, R L, A.N. Samaha, M. J. Keener, P. Chevez-Berrios, and J. D. Goosey. 2000. Corneal microsporidiosis: report of case, including electron microscopic observations. Ophthalmology 107: 1769–1775.

    PubMed  CAS  Google Scholar 

  • Franssen, F.F., J.T. Lumeij, and F. van Knapen. 1995. Susceptibility of Encephalitozoon cuniculi to several drugs in vitro. Antimicrobial Agents and Chemotherapy 39: 1265–8.

    PubMed  CAS  Google Scholar 

  • Franzen, C., D. A Schwartz, G. S. Visvesvara, A. Muller, A. Schwenk, B. Salzberger, G. Fatkenheuer, P. Hartmann, G. Mahrle, and V. Diel. 1995. Immunologically confirmed disseminated, asymptomatic Encephalitozoon cuniculi infection of the gastrointestinal tract in a patient with AIDS. Clinical of Infectious Disease 21: 1480–1484.

    CAS  Google Scholar 

  • Friedberg, D. N., and D. C. Ritterband. 1999. Ocular microsporidiosis. The microsporidia and microsporidiosis (Murray Wittner, editor, and Louis M. Weiss, contributing editor) American Society for Microbiology, Washington D.C.

    Google Scholar 

  • Field, A S, J. Marriot, S. T. Milliken, B. J. Brew, E. U. Canning, J. G. Kench, P. Darveniza, and J. L. Harkness. 1996. Myositis associated with a newly described microsporidian, Trachipleistophora hominis in a patient with AIDS. Journal of Clinical Microbiology 34: 2803–2811.

    PubMed  CAS  Google Scholar 

  • Frydman, N., and A. Valasinas. 1999. Polyamine based chemotherapy of cancer. Expert Opinion and Therapeutic Patents. 9: 1055–1068.

    CAS  Google Scholar 

  • Ghoda, L., D. Sidney, M. Macrae, and P. Coffino. 1992. Structural elements of ornithine decarboxylase required for intracellular degradation and polyamine-dependent regulation. Molecular and Cellular Biology 12: 2178–2185.

    PubMed  CAS  Google Scholar 

  • —, H.S. Basu, C.W. Porter, L.J. Marton, and P. Coffino. 1992. Role of ornithine decarboxylase suppression and polyamine depletion in the antiproliferative activity of polyamine analogs. Molecular Pharmacology 42: 302–306.

    PubMed  CAS  Google Scholar 

  • Goldberg, B., N. Yarlett, J. Sufrin, D. Lloyd, and C.J. Bacchi. 1997. A unique transporter of S-adenosylmethionine in African trypanosomes. FASEB Journal 11: 256–260.

    PubMed  CAS  Google Scholar 

  • Green, L.C., P.J. Didier, and E.S. Didier. 1999. Fractionation of sporogonial stages of the microsporidian Encephalitozoon cuniculi by Percoll gradients. Journal of Eukaryotic Microbiology. 46: 434–438.

    PubMed  CAS  Google Scholar 

  • Griffith E.C, Z. Su, B.E. Turk, S.P. Chen, Y.H. Chang, Z.C. Wu, K. Biemann, and J.O. Liu. 1997. Methionine aminopeptidase (type 2) is the common target of angiogenesis inhibitors AGM-1470 and ovalicin. Chemistry and Biology 4: 61–471.

    Google Scholar 

  • —, Z. Su, S. Niwayama, A. Ramsay, Y. Chang, and J. O. Liu. 1998. Molecular recognition of angiogenesis inhibitors fumagillin and ovalicin by methionine aminopeptidase 2. Proceedings of the National Academy of Sciences (USA) 95: 15183–15188.

    CAS  Google Scholar 

  • Gritz, D. C., D. S. Holsclaw, R. E. Neger, J. P. Whitcher Jr., and T. P. Margolis. 1997. Ocular and sinus microsporidial infection cured with systemic albendazole. American Journal of Ophthalmology 124: 241–243.

    PubMed  CAS  Google Scholar 

  • Guerrard, A., M. Rabodonirina, L. Cotte, O Liguory, M. A. Piens, S. Dauod, S. Picot, and J. L. Touranine. 1999. Intestinal microsporidiosis occurring in two renal transplant recipients treated with mycophenolate mofetil. Transplantation 68: 699–701.

    Google Scholar 

  • Gunnarsson, G., D. Hurlbut, P. C. DeGirolami, M. Federman, C. Wanke. 1995. Multiorgan microsporidiosis: report of five cases and review. Clinical Infectious Disease 21: 37–44.

    CAS  Google Scholar 

  • Han, C.K., S.K Ahn, N.S. Choi, R.K. Hong, S.K. Moon, H.S. Chun, S.J. Lee, J.W. Kim, C.I. Hong, D. Kim, J.H. Yoon, and K.T. No. 2000. Design and synthesis of highly potent fumagillin analogues from homology modeling for a human MetAP2. Bioorganic and Medicinal Chemistry Letters 10: 39–43.

    PubMed  CAS  Google Scholar 

  • Haque, A., W.S. Hollister, A. Willcox, and E.U. Canning. 1993. The antimicrosporidial activity of albendazole. Journal Invertebrate Pathology 62: 171–177.

    CAS  Google Scholar 

  • He, Y., T. Suzuki, and K. Kashiwagi. 1994. Antizyme delays the restoration by spermine of growth of polyamine-deficient cells through its negative regulation of polyamine transport. Biochemical and Biophysical Research Communications 203: 608–614.

    PubMed  CAS  Google Scholar 

  • Higgins, M. J., M. L. Kent, J. D. Moran, L.M. Weiss, S. C. Dawe. 1998. Efficacy of the fumagillin analog TNP-470 for Nucleospora salmonis and Loma salmonae infection in chinook salmon Oncorhynchus tsawytscha. Diseases of Aquatic Organisms 11: 45–49.

    Google Scholar 

  • Hirt, R. P., J. M. Logsdon, Jr., B. Healy, M.W. Dorey, W.F. Doolittle, and T.M. Embley, 1999. Microsporidia are related to Fungi: evidence from the largest subunit of RNA polymerase II and other proteins. Proceedings of the National Academy of Sciences (USA) 96: 580–585.

    CAS  Google Scholar 

  • Hu, R.H., and A.E. Pegg. 1997. Rapid induction of apoptosis by down regulated uptake of polyamine analogues. Biochemical Journal 328: 307–316.

    PubMed  CAS  Google Scholar 

  • Joste, N. E., J.D. Rich, K.J. Busam, and D.A. Schwartz. 1996. Autopsy verification of Encephalitozoon intestinalis (Microsporidiosis) eradication following albendazole therapy. Archives of Pathology and Laboratory Medicine 120: 199–203.

    PubMed  CAS  Google Scholar 

  • Kahn, I.A. J.D. Schwartzman, L.H. Kasper, and M. Moretto. 1999. CD8+ CTL’s are essential for protective immunity against Encepahlitozoon infection. Journal of Immunology 162: 6086–6091.

    Google Scholar 

  • Kano, T., and H. Fukui. 1982. Studies on Pleistophora infection in eel, Anguilla japonica —I. experimental induction of microsporidiosis and fumagillin efficacy. Fish Pathology 16: 193–200.

    Google Scholar 

  • —, T. Okauchi, and H. Fukui. 1982. Studies on Pleistophora infection in eel, Anguilla japonica — II. Preliminary tests for application of fumagillin. Fish Pathology 17: 107–114.

    CAS  Google Scholar 

  • Katinka, M.D., S. Duprat, E. Cornillot, G. Metenier, F. Thomarat, G. Prensier, V. Barbe, E. Peyretaillade, P. Brottier, P. Wincker, F. Delbac, H. El Alaoui, P. Peyret, W. Saurin, M. Gouy, J. Weissenbach, and C.P. Vivares. 2001. Genome sequence and gene compaction of the eukaryote parasite Encephalitozoon cuniculi. Nature 414: 450–453.

    PubMed  CAS  Google Scholar 

  • Katiyar, S.K., V.R. Gordon, G.L. McLaughlin, and T.D. Edlind. 1994. Antiprotozoal activities of benzimidazoles and correlations with B-tubulin sequence. Antimicrobial Agents and Chemotherapy 38: 2086–2090.

    PubMed  CAS  Google Scholar 

  • —, and T.D. Edlind. 1997. In vitro susceptibilities of the AIDS-associated microsporidian Encephalitozoon intestinalis to albendazole, its sulfoxide metabolite, and 12 additional benzimidazole derivatives. Antibicrobial Agents and Chemotherapy 41: 2729–2732.

    CAS  Google Scholar 

  • Katznelson, H., and C.A. Jamieson. 1953. Control of nosema disease of honeybees with fumagillin. Science 115: 70–71.

    Google Scholar 

  • Keeling, P.J., M.A. Luker, and J.D. Palmer. 2000. Evidence from beta-tubulin phylogeny that microsporidia evolved from within the fungi. Molecular Biology and Evolution 17: 23–31.

    PubMed  CAS  Google Scholar 

  • Keithly, J.S., G. Zhu, S.J. Upton, K.M. Woods, M.P. Martinez, and N. Yarlett. 1997. Polyamine biosynthesis in Cryptosporidian parvum and its implications for chemotherapy. Molecular Biochemical Parasitology 88: 35–42.

    PubMed  CAS  Google Scholar 

  • Kent, M.L., and S.C. Dawe. 1994. Efficacy of fumagillin DCH against experimentally induced Loma salmonae (Microsporea) infections in chinnok salmon Oncorhynchus tsawytscha. Diseases of Aquatic Organisms 20: 231–233.

    Google Scholar 

  • Kotler, D.P., and J.M. Orenstein. 1998. Clinical syndromes associated with microsporidiosis. Advances in Parasitology 40: 322–343.

    Google Scholar 

  • Lacey, E. 1990. Mode of action of benzimidazoles. Parasitology Today 6: 112–115.

    PubMed  CAS  Google Scholar 

  • Lauren, D.L., A. Wishkovsky, J.M. Groff, R.P. Hedrick, and D.E. Hinton. 1989. Toxicity and pharmacokinetics of the antibiotic fumagillin in yearling rainbow trout (Salmo gairdneri). Toxicology and Applied Pharmacology 98: 444–453.

    PubMed  CAS  Google Scholar 

  • Lecuit, M., E. Oksenhendler, and C. Sarfati. 1994. Use of albendazole for disseminated microsporidian infection in a patient with AIDS. Journal of Infectious Diseases 19: 332–333.

    CAS  Google Scholar 

  • Leder, K., N. Ryan, D. Spelman, and S.M. Crowe. 1998. Microsporidial disease in HIV-infected patients: A report of 42 patients and review of the literature. Scandinavian Journal of Infectious Diseases 30: 331–338.

    PubMed  CAS  Google Scholar 

  • Libby, P.R., M. Henderson, R.J. Bergeron, and C.W. Porter. 1989. Major increases in spermidine/spermine N 1-acetyltransferase activity by spermine analogues and their relationship to polyamine depletion and growth inhibition in L-1210 cells. Cancer Research 49: 6226–6231.

    PubMed  CAS  Google Scholar 

  • Liu, S., Widom, J., C.W. Kemp, C.M. Crews, and J. Clardy. 1998. Structure of human methionine aminopeptidase-2 complexed with fumagillin. Science 282: 1324–1327.

    PubMed  CAS  Google Scholar 

  • Lowther, W.T., D.A. McMillen, A.M. Orville, and B.W. Matthews. 1998. The anti-angiogenic agent fumagillin covalently modifies a conserved active-site histidine in the Escherichia coli methionine aminopeptidase. Proceedings of the National Academy Sciences (USA) 95: 12153–12157.

    CAS  Google Scholar 

  • Marton, L.J., and A.E. Pegg. 1995. Polyamines as targets for therapeutic intervention. Annual Review of Pharmacology and Toxicology 35: 55–91.

    PubMed  CAS  Google Scholar 

  • Merali, S., S. Muhamed, K. Chin, and A.B. Clarkson, Jr. 2000. Effect of a bis-benzyl polyamine analogue on Pneunocystis carinii. Antimicrobial Agents and Chemotherapy 44: 337–343.

    PubMed  CAS  Google Scholar 

  • Metcalf, B.W., P. Bey, C. Danzin, M.J. Jung, P. Casara, and J.P. Vevert. 1978. Catalytic irreversible inhibition of mammalian ornithine decarboxylase (E.C. 4.1.1.17) by substrate and product analogues. Journal of American Chemical Society. 100: 2551–2553.

    CAS  Google Scholar 

  • Metcalf, T.W., Doran, R.M.L., P..L Rowlands, A. Curry, and C.J.N. Lacey. 1992. Microsporidial keratoconjunctivitis in a patient with AIDS. British Journal of Ophthalmology 76: 177–178.

    Google Scholar 

  • Modigliani R, C. Bories, Y. Le Charpantier, M. Salmeron, B. Messing, A. Galian, J. C. Rambaud, A. Lavergne, B. Cochand-Priollet, and I. Desportes. 1985. Diarrhoea and malabsorption in Acquired Immune Deficiency Syndrome: a study of four cases with special emphasis on opportunisitic protozoan infestations. Gut 26: 179–187.

    PubMed  CAS  Google Scholar 

  • Molina, J.M., C. Chastang, J. Goguel, J.F. Michiels, C. Sarfati, I. Desportes-Livage, J. Horton, F. Derouin, and J. Modai. 1998. Albendazole for treatment and prophylaxis of microsporidiosis due to Encephalitozoon intestinalis in patients with AIDS: a randomized double-blind controlled trial. Journal of Infectious Diseases 177: 1373–1377.

    PubMed  CAS  Google Scholar 

  • —, J. Goguel, C. Sarfati, C. Chastang, I. Desportes-Livage, J.F. Michiels, C. Maslo, C. Katlama, L. Cotte, C. Leport, F. Raffi, F. Derouin, and J. Modai. 1997. Potential efficacy of fumagillin in intestinal microsporidiosis due to Enterocytozoon bieneusi in patients with HIV infection: results of a drug screening study. The French Microsporidiosis Study Group. AIDS 11: 1603–10.

    PubMed  CAS  Google Scholar 

  • —, —, —, J.F. Michiels, I. Desportes-Livage, S. Balkan, C. Chastang, L. Cotte, C. Maslo, A. Struxiano, F. Derouin, and J.M. Decazes. 2000. Trial of oral fumagillin for the treatment of intestinal microsporidiosis in patients with HIV infection. ANRS 054 Study Group. Agence Nationale de Recherche sur le SIDA. AIDS 14: 1341–1348.

    PubMed  Google Scholar 

  • —, —, —, C. Chastang, I. Desportes-Livage, J. F. Michiels, C. Maslo, C. Katlama, L. Cotte, C. Leport, F. Raffi, F. Derouin, and J. Modai. 1997. Potential efficacy of fumagillin in intestinal microsporidiosis due to Enterocytozoon bieneusi in patients with HIV infection: results of a drug screening study. AIDS 11: 1603–1610.

    PubMed  Google Scholar 

  • —, E. Oksenhendler, B. Beauvais, C. Sarfati, A. Jaccard, F. Derouin, and J. Modai. 1995. Disseminated microsporidiosis due to Septata intestinalis in patients with AIDS: clinical features and response to albendazole therapy. Journal of Infectious Diseases 171: 245–249.

    PubMed  Google Scholar 

  • —, Tourneur, M., C. Sarfari, S. Chevret, A. de Gouvello, J.G. Gobert, S. Balkan, and F. Deroun. 2002. Fumagillin treatment of intestinal microsporidiosis. New England Journal of Medicine 346: 1963–1969.

    Google Scholar 

  • Molnar, K., F. Baska, and C. Szekely. 1987. Fumagillin, an efficacious drug against renal sphaerosporosis of the common carp Cyprinus carpio. Diseases of Aquatic Organisms 2: 187–190.

    CAS  Google Scholar 

  • Moreto, M., I. Casciotti, B. Borell, and I.A. Khan. 2000. Lack of CD4+ T cells does not affect induction of CD8+ T-cell immunity against Encephalitozoon cuniculi infection. Infection and Immunity 68: 6223–6232.

    Google Scholar 

  • Murakami, Y., K. Tanakam, S. Matsufuji, Y. Miyazaki, and S. Hayashi. 1992. Antizyme, a protein induced by polyamines, accelerates the degradation of ornithine decarboxylase in Chinese-hamster ovary-cell extracts. Biochemical Journal 283: 661–664.

    PubMed  CAS  Google Scholar 

  • Orenstein, J.M., W. Steinberg, P.D. Smith, H. Rotterdam, and D.P. Kotler. 1990. Intestinal microsporidiosis as a cause of diarrhea in Human Immunodeficiency Virus-infected patients. Human Pathology 21: 475–481.

    PubMed  CAS  Google Scholar 

  • —, M. Tenner, A. Cali, and D.P. Kotler. 1992. A microsporidian previously undescribed in humans, infecting enterocytes and macrophages, and associated with diarrhea in an Acquired Immunodeficiency Syndrome patient. Human Pathology 23: 722–728.

    PubMed  Google Scholar 

  • Phillips, M.A., P. Coffino, and C.C. Wang. 1987. Cloning and sequencing of the ornithine decarboxylase gene from Trypanosoma brucei. Journal of Biological Chemistry 262: 8721–8727.

    PubMed  CAS  Google Scholar 

  • Pol, S., C.A. Romana, S. Richard, P. Amouyal, I. Desportes-Livage, F. Carnot, J. F. Pays, and P. Berthelot. 1993. Microsporidia infection in patients with the Human Immunodeficiency Virus and unexplained cholangitis. New England Journal of Medicine 328: 95–99.

    PubMed  CAS  Google Scholar 

  • Porter, C.W., B. Ganis, P.R. Libby, and R.J. Bergeron. 1991. Correlations between polyamine analog-induced increases in spermidine/spermine N 1-acetyltransferase activity and growth inhibition in human melanoma cell lines. Cancer Research 51: 3715–3720.

    PubMed  CAS  Google Scholar 

  • —, U. Regenass, and R.J. Bergeron. 1992. Polyamine inhibitors and analogues as potential anticancer agents. In: Polyamines in the gastrointestinal tract, Falk Symposium 62. R.H. Dowling, U.R. Folsch, and Chr. Loser (eds.) Kluwer Academic Publishers, Dordrecht pp. 301–322.

    Google Scholar 

  • Rabeneck, L., F. Gyorkey, R.M. Genta, P. Gyorkey, L.W. Foote, J.M.H. Risser. 1993. The role of Microsporidia in the pathogenesis of HIV-related chronic diarrhea. Annals of Internal Medicine 119: 895–899.

    PubMed  CAS  Google Scholar 

  • Rastrelli, P.D., E. Didier, and R.W. Yee. 1994. Microsporidial keratitis. Ophthalmology Clinics of North America 7: 617–633.

    Google Scholar 

  • Rosberger, D.F., O.N. Serdarevic, R.A. Erlandson, R.T. Bryan, D.A. Schwartz, G.S. Visvesvara, and P.C. Keenan. 1993. Successful treatment of microsporidial keratoconjunctivitis with topical fumagillin in a patient with AIDS. Cornea 12: 261–265.

    PubMed  CAS  Google Scholar 

  • Rossi, R.M., C. Wanke, and M. Federman. 1996. Microsporidian sinusitis in patients with the Acquired Immunodeficiency Syndrome. Laryngoscope 106: 966–971.

    PubMed  CAS  Google Scholar 

  • Rossi, P., Urbani, C., Gianfranco, D., and Pozio, E. 1999. Resolution of microsporidial sinusitis and keratoconjunctivitis by itraconazole treatment. American Journal of Ophthalmology 127: 210–212.

    PubMed  CAS  Google Scholar 

  • Sbottka, I., H. Albrecht, H. Schafer, J. Schottelius, G. S. Visvesvara, R. Laufs, and D. A. Schwartz. 1995. Disseminated Encephalitozoon (Septata) intestinalis infection in a patient with AIDS: novel diagnostic approaches and autopsy-confirmed parasitological cure following treatment with albendazole. Journal of Clinical Microbiology 33: 2948–2952.

    Google Scholar 

  • Schechter, P.J., and A. Sjoerdsma. 1989. Therapeutic utility of selected enzyme-activated irreversible inhibitors. In: Enzymes as targets for drug design. M.G. Palfreyman, P.P. McCann, W. Lovenberg, J.G. Temple, and A. Sjoerdsma (eds.) Academic Press, San Diego, pp. 201–210.

    Google Scholar 

  • Seiler N. 1995. Polyamine oxidase properties and functions. In Progress in brain research. P.M. Yu K.F. Tipton and A.A. Boulton eds. Progress in Brain Research 106: 333–3

    Google Scholar 

  • —, S. Sarhan, P. Mamont, P. Vasara, and C. Danzin. 1991. Some biological consequences of S-adenosylmethionine decarboxylase inhibition by MDL-73811. Life Chemistry Reports. 9: 151–162.

    Google Scholar 

  • Shadduck, J.A. 1980. Effect of fumagillin on in vitro multiplication of Encephalitozoon cunuculi. Journal Protozoology 27: 202–208

    CAS  Google Scholar 

  • Shantz, L.M., B.A. Stanley, J.A. Secrist, and A.E. Pegg. 1992. Purification of human S-adenosylmethionine decarboxylase expressed in Escherichia coli and use of this protein to investigate the mechanism of inhibition by the irreversible inhibitors, 5′-deoxy-5′-[(3-hydrazinopropyl)methylamino]adenosine and 5′{[(Z)-4-amino-2-butenyl]methylamino-5′ deoxyadenosine. Biochemistry 31: 6848–68

    PubMed  CAS  Google Scholar 

  • Sharpstone, D., A. Rowbottom, M. Nelson, and B. Gazzard. 1995. The treatment of microsporidial diarrhoea with thalidomide [letter]. AIDS 9: 658–659.

    PubMed  CAS  Google Scholar 

  • —, —, N. Francis, G. Tovey, D. Ellis, M. Barrett, and B. Gazzard. 1997. Thalidomide: a novel therapy for microsporidiosis [published erratum appears in Gastroenterology 1997 Sep;113(3):1054]. Gastroenterology 112: 1823–1829.

    PubMed  Google Scholar 

  • Silveira, H., E.U. Canning. 1995. Vittaforma corneae N. Comb. for the human microsporidium Nosema corneum Shadduck, Meccoli, Davis & Font, 1990, based on its ultrastructure in the liver of experimentally infected athymic mice. Journal of Eukaryotic Microbiology 42: 158–165.

    PubMed  CAS  Google Scholar 

  • Simon, D., L.M. Weiss, H.B. Tanowitz, A. Cali, J. Jones, and M. Winner. 1991. Light microscopic diagnosis of human microsporidiosis and variable response to octreotide. Gastroenterology 100: 271–273.

    PubMed  CAS  Google Scholar 

  • Sin, N., L. Meng,, M.Q.W. Wang, J.J. Wen, W.G. Bornmann, C. M. Crews. 1997. The antiangiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2. Proceedings of the National Academy of Sciences (USA) 94: 6099–6103.

    CAS  Google Scholar 

  • Soule, J.B., A.L. Halverson, R.B. Becker, M.C. Pistole, and J.M. Orenstein. 1997. A patient with Acquired Immunodeficiency Syndrome and untreated Encephalitozoon (Septata) intestinalis microsporidiosis leading to small bowel perforation: response to albendazole. Archives of Pathology and Laboratory Medicine 121: 880–887.

    PubMed  CAS  Google Scholar 

  • Sprague, V., J.J. Becnel, and E.I Hazard. 1992. Taxonomy of phylum Microspora. Critical Reviews in Microbiology 18: 285–395.

    PubMed  CAS  Google Scholar 

  • Taylor, A. 1993. Aminopeptidases: structure and function. FASEB Journal 7: 290–298

    PubMed  CAS  Google Scholar 

  • Terada, S., K. Rajender Reddy, L.J. Jeffers, A. Cali, and E. Schiff. 1987. Microsporidian hepatitis in the Acquired Immunodeficiency Syndrome. Annals of Internal Medicine 107: 61–62.

    PubMed  CAS  Google Scholar 

  • Valasinas, A., A. Sarkar, V.K. Reddy, L.J. Marton, H.S. Basu, and B. Frydman. 2001. Conformationally restricted analgoues of N 1,N 14 Bis(ethyl)homospermine (BE-4-4-4-4): synthesis and growth inhibitory effects on human prostate cancer cells. Journal of Medicinal Chemistry 44: 390–403.

    PubMed  CAS  Google Scholar 

  • Vavra, J., A., T. Yachnis, J.A. Shadduck, and J. M. Orenstein. 1998. Microsporidia of the genus Trachipleistophora—causative agents of human microsporidiosis: description of Trachipleistophora anthropophthera n. sp. (Protozoa: Microsporidia). Journal of Eukaryotic Microbiology 45: 273–83.

    PubMed  CAS  Google Scholar 

  • Visvesvara, G.S., G.J. Leitch, H. Moura, S. Wallace, R. Weber, and R.T. Bryan. 1991. Culture, electron microscopy and immunoblot studies on a microsporidian parasite isolated from the urine of a patient with AIDS. Journal of Protozoology 38: 105S–111S.

    PubMed  CAS  Google Scholar 

  • —, —, A.J. da Silva, G.P. Croppo, H. Moura, S. Wallace, S.B. Slemenda, D.A. Schwartz, D. Moss, and R.T. Bryan 1994. Polyclonal and monoclonal antibody and PCR-amplified small-subunit rRNA identification of a microsporidian, Encephalitozoon hellem, isolated from an AIDS patient with disseminated infection. Journal of Clinical Microbiology 32: 2760–2768.

    PubMed  Google Scholar 

  • Vujcic, S., P. Diegelman, C.J. Bacchi, D.L. Kramer, and C.W. Porter. 2002. Identification and characterization of novel mammalian spermine oxidase. Biochemical Journal 367: 665–675.

    PubMed  CAS  Google Scholar 

  • Waters, R.W., B. Frydman, L.J. Marton, A. Valasinas, V.K. Reddy, J.A. Harp, M.J. Wannemuehler, and N. Yarlett. 2000. [′N, 12 N]bis(ethyl)-Cis-6,7-dehydrospermine: a new drug for treatment and prevention of Cryptosporidium parvum infection of mice deficient in T-cell receptor Alpha. Antimicrobial Agents and Chemotherapy 44: 2891–2894.

    PubMed  CAS  Google Scholar 

  • Weber, R., R.T. Bryan, R.L. Owen, C.M. Wilcox, I. Gorelkin, and G.S. Visvesvara. 1992. Improved light-microscopical detection of microsporidia spores in stool and duodenal aspirates. New England Journal of Medicine 326: 161–166.

    PubMed  CAS  Google Scholar 

  • —, P. Deplazes, M. Flepp, et al. 1997. Cerebral microsporidiosis due to Encephalitozoon cuniculi in a patient with Human Immunodeficiency Virus infection. New England Journal of Medicine 336: 474–478.

    PubMed  CAS  Google Scholar 

  • —, M. Flepp, and W. Wichmann. 1997. Cerebral microsporidiosis due to Encephalitozoon cunuculi — reply to letter. New England Journal of Medicine 337: 640–641.

    Google Scholar 

  • —, B. Sauer, M.A. Spycher, P. Deplazes, R. Keller, R. Ammann, J. Briner, and R. Luthy. 1994. Detection of Septata intestinalis in stool specimens and coprodiagnostic monitoring of successful treatment with albendazole. Clinical and Infectious Disease 19: 342–345.

    CAS  Google Scholar 

  • Weiss, L.M., S.F. Costa, and H. Shang. 2001. Microsporidian methionine aminopeptidase type 2. Journal of Eukaryotic Microbiology Suppl:88–90S.

    Google Scholar 

  • —, E. Michalakakis, C.M. Coyle, H.B. Tanowitz, and M. Wittner. 1994. The activity of albendazole against Encephalitozoon cuniculi. Journal of Eukaryotic Microbiology 41: S65.

    Google Scholar 

  • —, T.D. Edlind, C.R. Vossbrinck, and T. Hashimoto. 1999. Microsporidian molecular phytogeny: the fungal connection. Journal of Eukaryotic Microbiology 46: 17S–18S.

    PubMed  CAS  Google Scholar 

  • —, and C.R. Vossbrinck 1998. Microsporidiosis: molecular and diagnostic aspects. Advances in Parasitology 40: 351–395.

    PubMed  CAS  Google Scholar 

  • Wittner, M., and L.M. Weiss (eds). 1999. The Microsporidia and Microsporidiosis. ASM Press. Washington DC.

    Google Scholar 

  • Xiao, L. and R.A. Casero. 1995. Regulation of spermidine/spermine N’-acetyltransferase. In: Polyamines: regulation and molecular interaction. R.A. Casero (ed.) pp. 77–98. Springer-Verlag, New York.

    Google Scholar 

  • Yarlett, N., and C.J. Bacchi. 1988. Effect of DL-α-difluoromethylornithine on polyamine synthesis and interconversion in Trichomonas vaginalis grown in a semi defined medium. Molecular and Biochemical Parasitology 31: 1–10.

    PubMed  CAS  Google Scholar 

  • Yee, R.W., F.O. Tio, J. A. Martinez, K. S. Held, J. A. Shadduck, and E.S. Didier. 1991. Resolution of microsporidial epithelial keratopathy in a patient with AIDS. Ophthalmology 98: 196–201.

    PubMed  CAS  Google Scholar 

  • Yokoyama, H., K. Ogawa, and H. Wakabayashi. 1990. Chemotherapy with fumagillin and toltrazuril against kidney enlargement disease of goldfish caused by the myxosporean Hoferellus carassii. Fish Pathology 25: 157–163.

    Google Scholar 

  • Zender, H.O, E. Arrigoni, J. Echert, and Y. Kapanici. 1989. A Case of Encephalitozoon cuniculi peritonitis in a patient with AIDS. American Journal of Clinical Pathology 92: 352–356.

    PubMed  CAS  Google Scholar 

  • Zou, Y., Z. Wu, N. Sirisoma, P.M. Woster, R.A. Casero, L.M. Weiss, D. Rattendi, S. Lane, and C.J. Bacchi. 2001. Novel alkylpolyamine analogues that possess both antiparasitic and antimicrosporidial activity. Bioorganic and Medicinal Chemistry Letters 11: 1613–1617.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biology, Haskins Laboratory, Pace University, New York, New York, US

    C. J. Bacchi

  2. Departments of Pathology and Medicine, Albert Einstein College of Medicine, Bronx, New York, USA

    L. M. Weiss

Authors
  1. C. J. Bacchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. M. Weiss
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg, Virginia, USA

    David S. Lindsay

  2. Albert Einstein College of Medicine, Bronx, New York, USA

    Louis M. Weiss

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Kluwer Academic Publishers

About this chapter

Cite this chapter

Bacchi, C.J., Weiss, L.M. (2004). Chemotherapy of microsporidiosis: Benzimidazoles, fumagillin and polyamine analogues. In: Lindsay, D.S., Weiss, L.M. (eds) Opportunistic Infections: Toxoplasma, Sarcocystis, and Microsporidia. World Class Parasites, vol 9. Springer, Boston, MA. https://doi.org/10.1007/978-1-4020-7846-0_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-4020-7846-0_10

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4020-7814-9

  • Online ISBN: 978-1-4020-7846-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation