Energy metabolism of adult Haemonchus contortus in vitro: a comparison of benzimidazole-susceptible and -resistant strains.
In vitro biochemical characteristics of three strains of Haemonchus contortus, benzimidazole-susceptible, mebendazole-resistant and thiabendazole-resistant isolates, were investigated. Steady-state pool sizes of glucose and metabolic intermediates, including adenine nucleotides and end-products revealed no differences between adult worms resistant or susceptible to benzimidazoles in 30-60 min incubations. Possible regulatory steps in the glycolytic pathway are identified as those involving the enzymes hexokinase, phosphofructokinase and pyruvate kinase. The major component of carbohydrate reserves was trehalose, some glycogen was present and the glucose pool was small. On incubation for 18 h in vitro, carbohydrates were metabolised in all three strains. However, in the benzimidazole-susceptible worms there was a preferential use of the glycogen reserves to maintain energy metabolism. All three strains had similar levels of total lipid, total protein and free amino acid and these did not change on incubation. The major products found in the medium on incubation, in vitro, for 18 h were propionate, acetate and propanol, with smaller amounts of ethanol, lactate and malate. All three strains produced a similar sum total of end-products; however, in the mebendazole-resistant strain there appeared to be a diversion of carbon flow to the ethanol-producing pathway. Carbon dioxide production in 60 min incubations was measured using radioactively labelled glucose. A greater output of labelled CO2 was noted under aerobic than anaerobic conditions. This was particularly true of the mebendazole-resistant strain and, in this strain, was sensitive to cyanide. The extent to which metabolic differences noted in the three strains may be related to benzimidazole resistance is not readily apparent.
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D050260:Carbohydrate Metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D004351:Drug Resistance; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006189:Haemonchus / Q000187:drug effects / Q000378:metabolism*; D050356:Lipid Metabolism; D011190:Potassium Cyanide / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D014199:Trehalose / Q000378:metabolism; D014251:Trichostrongyloidea / Q000378:metabolism*
D000596:Amino Acids; D001562:Benzimidazoles; D011506:Proteins; D002245:Carbon Dioxide; D006003:Glycogen; D014199:Trehalose; C031000:benzimidazole; D005947:Glucose; D011190:Potassium Cyanide