Enzymatic Studies on the Mechanism of the Resistance of Pneumococcus to Drugs

Publisher Website
Google Scholar
Abstract
The effects of acriflavine, atabrine, propamidine, optochin, and sulfonamides on the dehydrogenase activities of pneumococci (types I, n, and HI) in the presence of glucose, hexose diphosphate (HDP), glycerol, lactate, and ethyl alcohol were investigated. The glucose dehydrogenase activities of the parent susceptible pneumococci were inhibited by all the drugs except sulf onamides. This effect has been found to be due to a competition between sulfathiazole and methylene blue. Dehydrogenase activity is less inhibited in the presence of HDP than in the presence of glucose by acridines and optochin, and it is not at all affected by propamidine. Ethyl alcohol dehydrogenase activity is also little affected by propamidine but is inhibited by the acridines and optochin. Glycerol and lactate activity are only slightly affected. The degrees of inhibition by drugs are related to the control activities of the organisms, the no. of organisms present in the systems, and, in the case of glucose, the substrate concn. Drug-resistant pneumococci are less subject to the inhibition of their glucose dehydrogenase activity by the resp. drugs than are the corresponding susceptible parent strains. A cross resistance to inhibition of glucose dehydrogenase exists between organisms made resistant to the acridines and to propamidine. Riboflavin can counteract the inhibitory effect of acriflavine and atabrine on the growth of the susceptible organisms. It is only slightly antagonistic to propamidine and optochin in the same systems and not at all to sulf onamides. The inhibition of glucose dehydrogenase activity by the acridines and propamidine is also relieved by the presence of riboflavin, but not by nicotinamide or thiamine. The inhibition of the glucose dehydrogenase by optochin is unaffected by any of the vitamins. The findings are analyzed in relation to similarity of the physical properties and action of structurally dissimilar acridines and propamidine; the effects of these drugs on dehydrogenases in relation to their mode of antibacterial action; and the antagonism of riboflavin to inhibition by the drugs.