Theoretical aspects of enzyme induction and inhibition leading to the reversal of resistance to biocides.
The well-known phenomena of enzyme induction and inhibition have been applied in the enunciation of two mechanisms which could be used in the reversal of resistance which organisms develop towards biocides (drugs and pesticides) in many cases. For those biocides active per se which are metabolized by inducible enzymes to non-toxic metabolites, resistant organisms would be those possessing high levels of drug-metabolizing enzymes (Mechanism 1). For those biocides inactive per se but requiring metabolic activation for activity, resistant organisms would be those possessing low levels of drug metabolizing enzymes (Mechanism 2). In mechanism 1, the addition of enzyme inhibitors to the biocide would be effective in reversing resistance. In mechanism 2 the addition of an enzyme inducer to the biocide would increase the susceptibility of the resistant organisms. An ectoparasite insecticide 2-chloro-1-(2,4 dichlorophenyl) vinyl diethylphosphate (chlorfenvinphos or supona) is used as an example for mechanism 1. The malarial drugs primaquine and chloroquine are used as examples of mechanism 2.
D000328:Adult; D055598:Chemical Phenomena; D002621:Chemistry; D002648:Child; D002709:Chlorfenvinphos / Q000378:metabolism; D002738:Chloroquine / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System; D004351:Drug Resistance; D004790:Enzyme Induction; D004798:Enzymes / Q000378:metabolism*; D005260:Female; D006801:Humans; D008288:Malaria / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D010105:Oxygenases / Q000378:metabolism; D010575:Pesticides / Q000378:metabolism*; D011247:Pregnancy; D011319:Primaquine / Q000378:metabolism
D004798:Enzymes; D010575:Pesticides; D002738:Chloroquine; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D002709:Chlorfenvinphos; D011319:Primaquine