ENZYMATIC STUDIES ON THE MECHANISM OF THE RESISTANCE OF PNEUMOCOCCUS TO DRUGS I. STUDIES OF THE DEHYDROGENASE ACTIVITIES AND INTERRELATIONSHPS OF PNEUMOCOCCI SUSCEPTIBLE AND RESISTANT TO ACRIFAVINE,

Despite the nuimerous studies for over fifty years on the resistance manifested by microorganisms to various drugs, a satisfactory concept concerning the bio-chemical mechanism of resistance development has not as yet evolved. The many observations that suggest a correlation between flavoprotein activity and the acquisition of resistance to certain drugs have been analyzed by one of us (Sevag, 1946). The studies here presented were oriented toward an experimental elucidation of these observations. The pneumococcus was used in these investigations sinceit represents a patho-genic organism whose respiratory activities are principally dependent on the flavoprotein enzymes (Avery and Neill, 1924; Sevag, 1933; Sevag and Maiweg, 1934; Sevag and Shelburne, 1942). Strains of three different serological types (I, II, and III) were made resistant independently to each of five different drugs by subjecting the organisms to increasing concentrations of the drugs in vitro. The resistant strains and their susceptible parent strains were studied for their dehydrogenase activities using methylene blue as the hydrogen acceptor to meas