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Quinacrine-resistant Giardia duodenalis

Published online by Cambridge University Press:  06 April 2009

J. A. Upcroft
Affiliation:
The Queensland Institute of Medical Research, Bancroft Center, 300 Herston Road, Brisbane, Queensland 4029, Australia
R. W. Campbell
Affiliation:
The Queensland Institute of Medical Research, Bancroft Center, 300 Herston Road, Brisbane, Queensland 4029, Australia
P. Upcroft
Affiliation:
The Queensland Institute of Medical Research, Bancroft Center, 300 Herston Road, Brisbane, Queensland 4029, Australia

Summary

Quinacrine resistance has been induced in 3 Giardia duodenalis laboratory stocks and 4 lines resistant to other drugs. The quinacrine-resistant lines were maintained in normally lethal levels of 5 µM quinacrine and some lines are viable in 20 µM levels of the drug. Fluorescence studies indicated that quinacrine was taken up by sensitive cells but was actively excluded from resistant trophozoites. The nuclei were not a site of drug accumulation and no specific fluorescence in the trophozoite could be attributed to any structure. Blebs of concentrated drug appeared prior to disintegration of the membrane of drug-sensitive trophozoites exposed to drug overnight. Parasite lines already resistant to furazolidone adapted more readily to quinacrine exposure than drug-sensitive stocks. This multiple drug resistant phenotype was not as marked with metronidazole-resistant lines.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1996

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References

REFERENCES

Al-Karawi, M., Salam, I. & Mohamed, A. E. (1988). Combined oral and endoscopic mepacrine therapy in a case of persistent chronic symptomatic giardiasis. Transactions of the Royal Society of Tropical Medicine and Hygiene 82, 581.CrossRefGoogle Scholar
Boreham, P. F. L. (1991). Giardiasis and its control. Pharmacology Journal 234, 271–4.Google Scholar
Boreham, P. F. L. (1995). Dreamtime, devastation and deviation: Australia's contribution to the chemotherapy of human parasitic infections. International Journal for Parasitology 25, 1009–22.CrossRefGoogle Scholar
Boreham, P. F. L., Phillips, R. E. & Shepherd, R. W. (1984). The sensitivity of Giardia intestinalis to drugs in vitro. Journal of Antimicrobial Chemotherapy 14, 449–61.CrossRefGoogle ScholarPubMed
Boreham, P. F. L., Phillips, R. E. & Shepherd, R. W. (1985). A comparison of the in vitro activity of some 5-nitroimidazoles and other compounds against Giardia intestinalis. Journal of Antimicrobial Chemotherapy 16, 589–95.CrossRefGoogle ScholarPubMed
Brown, D. M., Upcroft, J. A. & Upcroft, P. (1995). Free radical detoxification in Giardia duodenalis. Molecular and Biochemical Parasitology 72, 4756.CrossRefGoogle ScholarPubMed
Capon, A. G., Upcroft, J. A., Boreham, P. F. L., Cottis, L. E. & Bundesen, P. G. (1989). Similarities of Giardia antigens derived from human and animal sources. International Journal for Parasitology 19, 91–8.CrossRefGoogle ScholarPubMed
Craft, J. C. (1986). Evaluation of anti-Giardia lamblia chemotherapy in the rat model of giardiasis. In Experimental Models in Antimicrobial Chemotherapy, Vol. 3 (ed. Zak, O. & Sande, M. A.), pp. 173–84. London: Academic Press.Google Scholar
Crouch, A. A., Seow, W. K. & Thong, Y. H. (1986). Effect of twenty-three chemotherapeutic agents on the adherence and growth of Giardia lamblia in vitro. Transactions of the Royal Society of Tropical Medicine and Hygiene 80, 893–6.CrossRefGoogle ScholarPubMed
Crowe, R. & Whitear, M. (1978). Quinacrine fluorescence of Merkel cells in Xenopus laevis. Cell and Tissue Research 190, 273–83.CrossRefGoogle ScholarPubMed
Fairley, N. H. (1946). Atebrin susceptibility of the Aitaipe-Wewak strains of P. falciparum and P. vivax – a field and experimental investigation by L.H.Q. Medical Research Unit, Cairns. Transactions of the Royal Society of Tropical Medicine and Hygiene 40, 229–67.Google Scholar
Favennec, L., Chochillin, C., Magne, D., Meillet, D., Raichvarg, D., Savel, J. & Gobert, J. G. (1992). A new screening assay for antigiardial compounds: effect of various drugs on the adherence of Giardia duodenalis to Caco2 cells. Parasitology Research 78, 80–1.CrossRefGoogle ScholarPubMed
Geary, T. G., Divo, A. A. & Jensen, J. B. (1987). Activity of quinoline-containing antimalarials against chloroquine-sensitive and-resistant strains of Plasmodium falciparum in vitro. Transactions of the Royal Society of Tropical Medicine and Hygiene 81, 499503.CrossRefGoogle ScholarPubMed
Gillin, F. D. & Diamond, L. S. (1981). Inhibition of clonal growth of Giardia lamblia and Entamoeba histolytica by metronidazole, quinacrine and other antimicrobial agents. Journal of Antimicrobial Chemotherapy 8, 305–16.CrossRefGoogle ScholarPubMed
Hartman, H. R. & Kyser, F. A. (1941). Giardiasis and its treatment. Journal of the American Medical Association 116, 2835–9.CrossRefGoogle Scholar
Inge, P. M. G. & Farthing, M. J. G. (1987). A radiometric assay for antigiardial drugs. Transactions of the Royal Society of Tropical Medicine and Hygiene 81, 345–7.CrossRefGoogle ScholarPubMed
Jensen, J. B. & Trager, W. (1977). Plasmodium falciparum in culture: use of outdated erythrocytes and description of the candle jar method. Journal of Parasitology 63, 883–6.CrossRefGoogle ScholarPubMed
Lapierre, J., Bougnoux, M. E. & Dupouy-Camet, J. (1985). Intérêt de la mépacrine dans le traitement des giardiases rebelles. La Presse Médicale 14, 1667.Google Scholar
Martin, C. (1962). Utilisation du Flagyl (8823RP) dans le traitmant de la lambliase de l'enfant. Journal de Médecine de Bordeaux et du Sud-Ouest 139, 1766–8.Google Scholar
Nikaido, H. (1994). Prevention of drug access to bacterial targets: permeability barriers and active efflux. Science 264, 382–8.CrossRefGoogle ScholarPubMed
Peters, w. (1966). Drug responses of mepacrine- and primaquine-resistant strains of Plasmodium berghei, Vincke and Lips, 1948. Annals of Tropical Medicine and Parasitology 60, 2530.CrossRefGoogle ScholarPubMed
Phillips, R. E., Boreham, P. F. L. & Shepherd, R. W. (1984). Cryopreservation of viable Giardia intestinalis trophozoites. Transactions of the Royal Society of Tropical Medicine and Hygiene 78, 604–6.CrossRefGoogle ScholarPubMed
Rowedder, A., Meier, R., Wegmann, W. & Gyr, K. (1991). Combined oral and endoscopic mepacrine therapy in therapy-resistant symptomatic giardiasis. Schweizerische Medizinische Wochenschrift 121, 1383–6.Google ScholarPubMed
Sears, S. D. & O'Hare, J. (1988). In vitro susceptibility of Trichomonas vaginalis to 50 antimicrobial agents. Antimicrobial Agents and Chemotherapy 32, 144–6.CrossRefGoogle ScholarPubMed
Taylor, G. D., Wenman, W. M. & Tyrrell, D. L. J. (1987). Combined metronidazole and quinacrine hydrochloride therapy for chronic giardiasis. Canadian Medical Association Journal 136, 1179–80.Google ScholarPubMed
Townson, S. M., Laqua, H., Upcroft, P., Boreham, P. F. L. & Upcroft, J. A. (1992). Induction of metronidazole and furazolidone resistance in Giardia. Transactions of the Royal Society of Tropical Medicine and Hygiene 86, 521–2.CrossRefGoogle ScholarPubMed
Townson, S. M., Boreham, P. F. L., Upcroft, P. & Upcroft, J. A. (1994 a). Resistance to the nitroheterocyclic drugs. Acta Tropica 56, 173–94.CrossRefGoogle Scholar
Townson, S. M., Hanson, G. R., Upcroft, J. A. & Upcroft, P. (1994 b). A purified ferredoxin from Giardia duodenalis. European Journal of Biochemistry 220, 439–46.CrossRefGoogle ScholarPubMed
Upcroft, J. A., Boreham, P. F. L., Campbell, R. W., Shepherd, R. W. & Upcroft, P. (1995). Biological and genetic analysis of a longitudinal collection of Giardia samples derived from humans. Acta Tropica 60, 3546.CrossRefGoogle ScholarPubMed
Upcroft, P. (1994). Multiple drug resistance in the pathogenic protozoa. Acta Tropica 56, 195212.CrossRefGoogle ScholarPubMed
Warhurst, D. C. (1986). Antimalarial drugs: mode of action and resistance. Journal of Antimicrobial Chemotherapy 18 Suppl. B, 51–9.CrossRefGoogle ScholarPubMed
Warhurst, D. C. & Thomas, S. C. (1975). Localisation of mepacrine in Plasmodium berghei and Plasmodium falciparum by fluorescence microscopy. Annals of Tropical Medicine and Parasitology 69, 417–20.CrossRefGoogle Scholar
Zamora, J. M., Pearce, H. L. & Beck, W. T. (1988). Physical-chemical properties shared by compounds that modulate multidrug resistance in human leukemic cells. Molecular Pharmacology 33, 454–62.Google ScholarPubMed
Zidovetzki, R., Sherman, I. W., Atiya, A. & De Boeck, H. (1989). A nuclear magnetic resonance study of the interactions of the antimalarials chloroquine, quinacrine, quinine and mefloquine with dipalmitoylphosphatidylcholine bilayers. Molecular and Biochemical Parasitology 35, 199208.CrossRefGoogle ScholarPubMed