The effects of saturated fatty acids on Giardia duodenalis trophozoites in vitro

Abstract

Giardia duodenalis is a protozoal, intestinal parasite that is a common aetiological agent of infectious diarrhoea in humans worldwide. Chemotherapeutic intervention presently offers a limited range of drugs and these are usually only employed after clinical diagnosis. Moreover, these drugs are ineffective against the infectious cysts, can produce unpleasant side effects, and are expensive with limited availability in developing countries. Frequent reports of drug toxicity, treatment failure and parasite drug resistance have, in some instances, also resulted in the increasing reluctance to over-prescribe synthetic anti-microbials. Alternatively, there is now mounting evidence to suggest that some of the naturally derived, medium-chain, saturated fatty acids (MCSFAs) possess anti-microbial and anti-parasitic properties. We have therefore examined the effects of four different fatty acids on G. duodenalis trophozoites in vitro. Cytotoxicity was determined using fluorescence, scanning and transmission electron microscopic techniques and standard cytotoxicity assays. Our studies have confirmed that the MCSFA, dodecanoic acid (C: 12) (common name: lauric acid), is anti-giardial, with an LD50 concentration comparable to that of metronidazole, the drug of choice in the treatment of giardiasis. Dodecanoic acid appeared to induce trophozoite death by accumulating within the parasite cytoplasm resulting in rupture of the cell membrane. This study has opened fresh avenues for development of natural drug therapy in which food supplementation may augment, or even replace, some of the standard chemotherapeutic agents presently employed in the treatment of giardiasis and possibly other infectious intestinal diseases.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

References

  1. Adam RD (1991) The biology of Giardia species. Microbiol Rev 55(4):706–732

    CAS  PubMed  Google Scholar 

  2. Barr SC, Bowman DD (1994) Giardiasis in dogs and cats. Compendium Contin Educ Practicing Vet 16:603–610

    Google Scholar 

  3. Barr SC, Bowman DD, Heller RL, Erb HN (1993) Efficiency of albendazole against giardiasis in dogs. Am J Vet Res 54:926–928

    CAS  PubMed  Google Scholar 

  4. Berggson G, Arnfinnsson J, Karlsson SM, Steingrimsson O, Thomar H (1998) In vitro inactivation of Chlamydia trachomatis by fatty acid acids and monoglycerides. Antimicrob Agents Chemother 43(11):3209–3212

    Google Scholar 

  5. Berggson G, Steingrimsson O, Thormar H (1999) In vitro susceptibilities of Neisseria gonorrhoea to fatty acids and monoglycerides. Antimicrob Agents and Chemother 43(11):2790–2792

    Google Scholar 

  6. Bergogne-Berezin E, Courvalin P, Gehanno P, Demaresy J, Perronne C, Duchuzeau R (1998) Forum on bacterial resistance. La Presse Medicale 27(35):1796–1800

    CAS  PubMed  Google Scholar 

  7. Boddie RL, Nickerson SC (1992) Evaluations of post milking teat germicides containing lauricidin, saturated fatty acid and lactic acid. J Dairy Sci 75:1725

    CAS  PubMed  Google Scholar 

  8. Boreham PLF (1991) Giardiasis and its control. Pharm J 234:271–274

    Google Scholar 

  9. Boreham PLF (1994) The current status of chemotherapy for giardiasis. In: Thompson RCA, Reynoldson JA, Lymbery AJ (eds) Giardia from molecules to disease. Cab International, UK, pp 317–328

    Google Scholar 

  10. Boreham PLF, Phillip RE, Shepard RW (1988) Altered uptake of metronidazole in vitro by stocks of Giardia intestinalis with different drug sensitivities. Trans R Soc Trop Med Hyg 82:104–106

    Article  CAS  PubMed  Google Scholar 

  11. Box E (1981) Observation on Giardia in budgerigar. J Protozool 28:491–494

    CAS  PubMed  Google Scholar 

  12. Bugg RJ, Robertson ID, Elliot AD, Thompson RC (1999) Gastrointestinal parasites of urban dogs in Perth, Western Australia. Vet J 157(3):295–301

    Article  CAS  PubMed  Google Scholar 

  13. Buret A (1994) Pathogenesis: how does Giardia cause disease? In: Thomson RCA, Reynoldson JA, Lymbery AJ (eds) Giardia: from molecules to disease. CAB International, UK, pp 317–328

    Google Scholar 

  14. Buret A, denHollander N, Wallis PM, Befus D, Olson ME (1990) Zoonotic potential of giardiasis in domestic ruminants. J Infect Dis 162:231–238

    CAS  PubMed  Google Scholar 

  15. Christiaens TC, Digranes A, Baerheim A (2002) The relation between sale of antimicrobial drugs and antibiotic resistance in uropathogens in general practice. Scand J Prim Health Care 20(1):45–49

    Article  PubMed  Google Scholar 

  16. Christy P (1989) The Biology of Giardia in catchments and reservoir management. In: Wade A, Yapp G (eds) Giardia: an emerging issue in water management. Australian National University, Canberra, pp 88–93

    Google Scholar 

  17. Collyer R, Lim KH, Tang R, Prociv P (1992) Suburban dogs—a reservoir of human giardiasis. Med J Aust 156:814–815

    CAS  Google Scholar 

  18. Craft JC (1986) Evaluation of anti-Giardia lamblia chemotherapy in the rat model of giardiasis. Protozool Abstr 12

  19. Das S, Stevens T, Castillo C, Villasenor V, Arredondo H, Reddy K (2002) Lipid metabolism in mucous dwelling amitochondriate protozoa. Int J Parasitol 32:655–675

    Article  CAS  PubMed  Google Scholar 

  20. Delvinquier BJL, Jones MK (1988) Preliminary note on the intestinal flagellates of the Australian anura. Memoirs Qld Museum 25:333–334

    Google Scholar 

  21. Edlind TD, Hang TL, Chakraborty PR (1990) Activity of the anti-helminthic benzimidazoles against Giardia lamblia in vitro. J Infect Dis 162:1408–1411

    CAS  PubMed  Google Scholar 

  22. Erlandsen SL, Weisbrod AR, Knudson LW, Olereich R, Dodge WE, Jakubowski W, Bemrick WJ (1991) Giardiasis in the wild and captive bird population: high prevalence in herons and budgerigars. Int J Environ Health Res 1:132–143

    Google Scholar 

  23. Farbey MD, Reynoldson JA, Thompson RCA (1995) In vitro drug susceptibility of 29 isolates of G. duodenalis from humans as assessed by an adhesion assay. Int J Parasitol 25:594–599

    Google Scholar 

  24. Farthing MJG (1994) Giardiasis as a disease. In: Thomson RCA, Reynoldson JA, Lymbery AJ (eds) Giardia: from molecules to disease. CAB International, UK, pp 15–37

    Google Scholar 

  25. Fillippich LJ, McDonnell PA, Munoz E, Upcroft JA (1998) Giardia infection in budgerigars. Aust Vet J 76:246–249

    PubMed  Google Scholar 

  26. Flanagan PA (1992) Giardia—diagnosis, clinical course and epidemiology—a review. Epidemiol Infect 109:1–22

    CAS  PubMed  Google Scholar 

  27. Forshaw D, Palmer DG, Halse SA, Hopkins RM, Thomson RCA (1992) Giardia is straw-necked ibis (Threskiornis spinicollis) in Western Australia. Vet Rec 131:267–268

    CAS  PubMed  Google Scholar 

  28. Galbraith A, Bullock S, Manias E (1997) Fundamentals of pharmacology, 2nd edn. Addison-Wesley-Longman, Melbourne, Australia, pp 660–661

    Google Scholar 

  29. Gallagher AN, Gartrell BD, Upcroft JA (1995) Pathogenic Giardia isolates from a wild-trapped sulphur crested cockatoo (Cacatuagalerita). In: Proceedings of the Australian Committee of the Association of Avian Veterinarians, pp 267–268

  30. Gault MJ, Reiner DS, Gillin FD (1995) Tolerance of axenic cultivated entamoeba histolytica and Giardia lamblia to a variety of antimicrobial agents. Trans R soc Trop Med Hyg 79:60–62

    Google Scholar 

  31. Gillin FD, Reiner DS (1982) Attachment of the flagellate Giardia lamblia; role of reducing agents, serum, temperature, and ionic composition. Mol Cell Biol 2:369–377

    CAS  PubMed  Google Scholar 

  32. Gillin FD, Reiner DS, Wangs CS (1993a) Human milk kills parasitic intestinal protozoa. Science 2221:1290–1292

    Google Scholar 

  33. Gillin FD, Reiner DS, Wangs CS (1993b) Killing Giardia lamblia trophozoites by normal human milk. J Cell Biochem 45(8):236–351

    Google Scholar 

  34. Graczyk TK, Fayer R, Cranfield MR (1997) Zoonotic transmission of Cryptosporidium parvum: implications for waterborne cryptosporidiosis. Parasitol Today

    Google Scholar 

  35. Harris JC, Plummer S, Lloyd D (2001) Anti-giardial drugs. App Microbiol Biotechnol 57(5–6):614–619

    Article  CAS  Google Scholar 

  36. Hueston WJ, Dickerson L (2001) Antibiotic resistance and the need for the rational use of antibiotics. J Med Liban 49(5):246–256

    CAS  PubMed  Google Scholar 

  37. Isaacs CE, Thormar H (1991) The role of milk-derived antimicrobial lipids as antiviral and antibacterial agents. Adv Exp Med Biol 310:246–256

    Google Scholar 

  38. Isaacs CE, Kim KS, Thormar H (1994) Inactivation of enveloped viruses in human bodily fluids by purified lipids. Ann NY Acad Sci 724:475–484

    Google Scholar 

  39. Islam A (1990) Giardiasis in developing countries. In: Meyer EA (ed) Giardia. Elsevier, Amsterdam, pp 235–268

    Google Scholar 

  40. Itoh N, Muraoka N, Aoki M, Itagaki T (2001) Prevalence of Giardia lamblia infection in household dogs. Kansenshogaku Zasshi 75(8):671–677

    CAS  PubMed  Google Scholar 

  41. Jarroll EL (1994) Biochemical mechanism of anti-giardial drug action. In: Thompson RCA, Reynoldson JA, Lymbery AJ (eds) Giardia: from molecules to disease. Cab International, UK, pp 329–337

    Google Scholar 

  42. Kabara JJ (1978) The pharmacological effects of lipids. American Oil Chemists Society Press, Champaign, IL, pp 1–14

    Google Scholar 

  43. Kim KS, Isaacs CE, Thormar H (1994) The use of lipids antiviral compounds in lenti virus infections. Ann NY Acad Sci 724:489–491

    CAS  PubMed  Google Scholar 

  44. Kirkpatrick CE (1989) Giardiasis in large animals. Compendium Contin Educ Practicing Vet 11:80–84

    Google Scholar 

  45. Kirkpatrick CE, Skandm DL (1985) Giardiasis in a horse. J Am Vet Med Assoc 187:163–164

    CAS  PubMed  Google Scholar 

  46. Kortbeek LM, Limper L, Tolboom JJM, Naber AHJ (1994) Giardia lamblia resistance to nitroimidazole/albendazole therapy. In: Thompson RCA, Reynoldson JA, Lymbery AJ (eds) Giardia: from molecules to disease. CAB International, UK, p 374

    Google Scholar 

  47. Koudela B, Nohynkova E, Vitovec J, Pakandl M, Kulda J (1991) Giardia infections in pigs: detection and in vitro isolation of trophozoites of the Giardia intestinalis group. Parasitology 102:163–166

    PubMed  Google Scholar 

  48. Land KM, Johnson PJ (1999) Molecular basis of metronidazole resistance in pathogenic bacteria and protozoa. Drug Resist Updat 2(5):289–294

    Article  CAS  PubMed  Google Scholar 

  49. Lima A, More S, Barboza M, Soares A, Schleupner M, Newman R, Sears C, Nataro J, Fedorko D, Wuhib T, Schorling J, Guerrant R (2000) Persistent diarrhoea signals critical period of increased diarrhoea burdens and nutritional shortfalls; a prospective cohort study among children in north western Brazil. J Infect Dis 181(5):1643–1651

    Article  CAS  PubMed  Google Scholar 

  50. Lujan HD, Mowatt MR, Nash TE (1996) Lipid requirement and lipid uptake by Giardia lamblia trophozoite in culture. J Eukaryot Microbiol 43(3):237–242

    CAS  PubMed  Google Scholar 

  51. MacKerras MJ (1958) Australian mammals and their recorded internal parasites. In: Proceedings of the Linnaean Society of New South Wales, vol 83, pp 101–160

  52. Marino MR, Brown TJ (1992) Giardia intestinalis in North Island Possums, house mice and ship rats. N Z Vet J 40:24–27

    Google Scholar 

  53. McDonnell PA, Scott K, Teoh DA, Olson ME, Upcroft P, Upcroft JA, Buret A (2003) Infectivity and pathogenicity of a Giardia isolated from a wild, native parrot (Cacatua galerita) in domestic feline kittens and lambs. Vet Parasitol 111(1):31–46

    Article  CAS  PubMed  Google Scholar 

  54. McIntyre P, Boreham PLF, Phillips RE, Shepherd RW (1986) Chemotherapy in Giardiasis: clinical response and in vitro drug sensitivity of human isolates in axenic culture. J Paediatr 108:1005–1010

    CAS  Google Scholar 

  55. Meloni BP, Thompson RCA, Hopkins RM, Reynoldson JA, Gracey M (1993) The prevalence of Giardia and other intestinal parasites in children, dogs and cats from Aboriginal communities in Kimberly. Med J Aus 158:157–159

    CAS  Google Scholar 

  56. Neyts J, Kristmundsdottir T, De Clercq E, Thormar H (2000) Hydrogels containing monocaprin prevent intravaginal and intracutaneous infections with HSV-2 in mice. J Med Virol 61(1):107–110

    Article  CAS  PubMed  Google Scholar 

  57. O’Handley RM, Olson ME, McAllister TA, Morck DW, Jelinski M, Royan G, Cheng K-J (1997) Efficiency of fenbendazole for treatment of Giardiasis in calves. Am J Vet Res 58:384–388

    CAS  PubMed  Google Scholar 

  58. O’Handley RM, Olson ME, Fraser D, Adams P, Thompson RC (2000) Prevalence and genotypic characterization of Giardia in dairy calves from Western Australia and Western Canada. Vet Parasitol 90(3):193–200

    Article  CAS  PubMed  Google Scholar 

  59. Olson ME, Thorlakson CL, Desellier L, Morck DW, McAllister TA (1997a) Giardia and Cryptosporidium in Canadian farm animals. Vet Parasitol 68:375–381

    Article  CAS  PubMed  Google Scholar 

  60. Olson ME, Roach PD, Stabler M, Chan W (1997b) Giardiasis in ringed seals from the western Artic. J Wildl Dis 33:646–648

    CAS  PubMed  Google Scholar 

  61. Petschow BW, Batema RP, Ford LL (1996) Susceptibility of H. pylori to bactericidal properties of medium chain monoglycerides and free fatty acids. Antimicrob Agents Chemother 40(2):302–306

    CAS  PubMed  Google Scholar 

  62. Petschow BW, Batema RP, Talbott RD, Ford LL (1998) Impact of medium-chain monoglycerides on intestinal colonisation by Vibrio cholera or enterotoxigenic Escherichia coli. J Med Microbiol 47(5):383–389

    CAS  PubMed  Google Scholar 

  63. Reiner DS, Wang CS, Gillin FD (1986) Human milk kills Giardia Lamblia by generating toxic lipolytic products. J Infect Dis 154(5):825–832

    CAS  PubMed  Google Scholar 

  64. Reiner DS, McCaffery M, Gillin FD (1990) Sorting of cyst wall proteins to a regulated secretory pathway during differentiation of the primitive eukaryote, Giardia lamblia. Eur J Cell Biol 53:142–153

    CAS  PubMed  Google Scholar 

  65. Reynoldson JA (1994) New approaches in chemotherapy. In: Thompson RCA, Reynoldson JA, Lymbery AF (eds) Giardia: from molecules to disease. CAB International, UK, pp 339–355

    Google Scholar 

  66. Reynoldson JA, Thompson RCA, Meloni BP (1992a) The potential and possible mode of action of benzimidazoles against Giardia and other protozoa. J Pharm Med 2:35–50

    Google Scholar 

  67. Reynoldson JA, Thompson RCA, Horton RJ (1992b) Albendazole as a future anti-giardial agent. Parasitol Today B 412–413

  68. Robertson ID, Irwin PJ, Lymbery AJ, Thompson RC (2000) The role of companion animals in the emergence of parasitic zoonoses. Int J Parasitol 30(12–13):1369–1377

    Article  CAS  PubMed  Google Scholar 

  69. Rosenblatt JE (1992) Antiparasitic agents. Mayo Clin procedures 67(3):276–287

    CAS  Google Scholar 

  70. Ruest N, Faubert G (1995) Pathogenic potential of Giardia infection in cattle. Parasitol Today 11:184

    Article  Google Scholar 

  71. Sadeghi S, Wallace FA, Calder PC (1999) Dietary lipids modify the cytokine response to bacterial lipopolysaccharides in mice. Immunology 96(3):404–410

    Article  CAS  PubMed  Google Scholar 

  72. Seung-Ho O, Howard K (2000) A novel antibacterial agent derived from the C-terminal domain of Streptococcus mutans GTP-binding protein. J Antimicrob Chemother 46:95–99

    Article  PubMed  Google Scholar 

  73. Stevens TL, Gibson GR, Adam R, Maier J, Allison-Ennis M, Das S (1997) Uptake and cellular localization of exogenous lipids by Giardia lamblia—a primitive eukaryote. Exp Parasitol 86(2):133–143

    Article  CAS  PubMed  Google Scholar 

  74. Stewart J (1994) Ratites. In: Ritchie BW, Harrison GJ, Harrison LR (eds) Avian medicine: principles and application. Wingers Publications, Lake Worth, FL, pp 1284–1326

    Google Scholar 

  75. Sun CQ, O’Connor CJ, Robertson AM (2003) Antibacterial actions of fatty acids and monoglycerides against Helicobacter pylori. FEMS Immunol Med Microbiol 36(1–2):9–17

    Article  CAS  PubMed  Google Scholar 

  76. Swan JM, Thompson RC (1986) The prevalence of Giardia in dogs and cats in Perth, Western Australia. Aust Vet J 63:110–112

    CAS  PubMed  Google Scholar 

  77. Thompson RCA (1998) Giardia infections. In: Palmer SR, Lord Soulsby, Simpson DIH (eds) Zoonoses. Oxford University Press, Oxford, pp 546–561

    Google Scholar 

  78. Thompson RC (2000) Giardia as a re-emerging infectious disease and its zoonotic potential. Int J Parasitol 30(12–13):1259–1267

    Article  CAS  PubMed  Google Scholar 

  79. Thompson RCA, Reynoldson JA, Mendis AHW (1993) Giardia and Giardiasis. Adv Parasitol 32:71–160

    CAS  PubMed  Google Scholar 

  80. Thormar G, Isaacs CE, Kim KS, Brown HR (1994) Inactivation of visna virus and other enveloped viruses by free fatty acids and monoglycerides. Ann NY Acad Sci 724:465–471

    CAS  PubMed  Google Scholar 

  81. Tonks MC, Brown TJ, Ionas G (1991) Giardia infection of carts and dogs in New Zealand. N Z Vet J 39:33–34

    Google Scholar 

  82. Townson SM, Laqua H, Upcroft P, Boreham PLF, Upcroft JA (1992) Induction of metronidazole and furazolidone resistance in Giardia. Trans R Soc Trop Med Hyg 86:521–522

    Article  CAS  PubMed  Google Scholar 

  83. Ungar BLP (1990) Cryptosporidiosis in humans (Homo sapiens). In: Dubey JP, Speer CA, Fayer R (eds) Cryptosporidiosis of Man and Animals. CRC Press, Boston, pp 59–82

    Google Scholar 

  84. Upcroft JA, Upcroft P (1993) Drug resistance and Giurdia. Parasitol Today 9:187–190

    Article  CAS  PubMed  Google Scholar 

  85. Upcroft JA, Upcroft P (2001) Drug susceptibility testing of anaerobic protozoa. Antimicrob Agents Chemother 45(6):1819–1814

    Article  Google Scholar 

  86. Upcroft JA, Campbell RW, Upcroft P (1996) Quinacrine-resistant Giardia duodenalis. Parasitology 122:309–313

    Google Scholar 

  87. Vargas MH (2000) ED50Version 1.0 Instituto Nacional de Enfermedades Respiratorias

  88. Wang LL, Johnson EA (1992) Inhibition of Listeria monocytogenes by fatty acids and monoglycerides. Appl Environ Microbiol 58(2):624–629

    CAS  PubMed  Google Scholar 

  89. Winsland JKD, Nimmo S, Butcher PD, Farthing MJG (1989) Prevalence of Giardia in dogs and cats in the United Kingdom: survey of an Essex veterinary clinic. Trans R Soc Trop Med Hyg 83:791–792

    Article  CAS  PubMed  Google Scholar 

  90. Wolfe MS (1992) Giardiasis. Clin Microbiol Rev 5:93–100

    CAS  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Pauline Ann McDonnell.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Rayan, P., Stenzel, D. & McDonnell, P.A. The effects of saturated fatty acids on Giardia duodenalis trophozoites in vitro. Parasitol Res 97, 191–200 (2005). https://doi.org/10.1007/s00436-005-1432-5

Download citation

Keywords

  • Giardia duodenalis
  • Giardiasis
  • Dodecanoic acid
  • Lauric acid