Enzymatic studies on the mechanism of the resistance of pneumococcus to drugs. I. Studies of the dehydrogenase activities and interrelationships of pneumococci susceptible and resistant to acriflavine, atabrine, optochin, propamidine, and sulfonamide

In the preceding study (Gots and Sevag, 1948) it was shown that pneumococci made resistant to various drugs frequently possessed diminished dehydrogenase activities. It was suggested that the decreased dehydrogenase activity of the particular resistant organisms was a manifestation of a deficiency of susceptible sites, i.e., the resistant organisms depended on nonsusceptible metabolic sites for the maintenance of their physiological activities. The effect of the drugs on the dehydrogenase activity in the presence of the various substrates was therefore investigated to obtain information concerning these questions and to characterize certain of the enzymes involved in the production of the observed phenomena. Inhibition of Dehydrogenase Activity Methods and results. For the determination of the methylene-blue-reducing ability of the organisms a refinement of the technique used by Schnabel (1920) was used. This was substituted for the conventional Thunberg method, previ-ously used, in order to facilitate the performance of simultaneous experiments with several substrates and varying concentrations of drugs, organisms, and othe