Studies on Antibiotics and Enzyme Inhibitors

Abstract

I have been studying antibiotics since 1944. In 1951, pathogenic bacteria resistant to antibiotic drugs had not yet appeared, and it seemed that effective chemotherapy for all bacterial diseases except tuberculosis was a fait accompli. Therefore, I initiated screening for antibiotics active against tumors. Because streptomycin-resistant tubercle bacilli had caused difficulties, I also continued to screen for antibacterial antibiotics that would replace streptomycin in the treatment of tuberculosis. In 1956, my co-workers and I discovered kanamycin [1], an antibiotic useful in the treatment of streptomycin-resistant infections. A year later, when staphylococcal strains resistant to all drugs appeared, kanamycin was clinically tested for the treatment of disease caused by these strains. On July 10 and 11, 1958, a symposium on kanamycin was held by the New York Academy of Sciences in New York City. This meeting was presided over by Professor Maxwell Finland, who summarized the discussions and conclusions in the Annals of the New York Academy of Sciences [2]. The discovery of kanamycin stimulated and facilitated further studies of antibiotics in our laboratory. In 1966 we discovered bleomycin [3, 4]. The following year we elucidated the biochemical mechanism of resistance to aminoglycoside antibiotics and opened up an area of research in which the structures of the derivatives inhibiting resistant strains were predicted and chemically synthesized [5, 6]. Our group also undertook the screening of microbial culture filtrates for low-molecular-weight enzyme inhibitors [7-10]. At present, this field of study is increasing in importance. Extending our earlier work, we