Studies on the Mechanism of the Action of Sulfanilamide

Abstract
Summary: Experimental studies of the phagocytic and bactericidal actions of blood and serum should be so performed as to exclude the presence of even traces of added peptone-like material. When traces of peptone are present, sulfanilamide in concentrations similar to those occurring in the sera of treated patients produces morphological alterations of hemolytic streptococci in serum which are associated with diminished reproductive activity but not with bacterial death. In this form the streptococci are susceptible to destruction by phagocytes. Blood containing peptone and sulfanilamide may, therefore, be bactericidal. When peptone is excluded by washing the inoculum in serum or saline, sulfanilamide in the above concentrations will completely inhibit multiplication of young streptococci in serum, and sterility will frequently result within 24 hours if the inoculum is less than 5000 chains per cubic centimeter. Smears of the serum after sterilization has occurred suggest that lysis of the majority of the inoculated organisms has taken place. The population curve in any medium is a resultant of the combined activities of peptone and sulfanilamide, with these two reagents exercising opposing effects. A direct neutralization effect between these two substances has not been demonstrated. It is suggested that sulfanilamide prevents the specialized metabolic activity required of invasive organisms. The evidence so far obtained indicates that this effect may be achieved through prevention of the utilization of the protein substrate by the organisms.