Potentiated inhibition of Escherichia coli by certain combinations of agents.

Abstract

Much useful information has been obtained on the modes of action of chemotherapeutic agents, including tumor-inhibiting agents, by inhibition analysis in bacterial systems. In a number of cases the mode of action appears to be the same in bacterial and mammalian systems. Therefore, it is not unreasonable to test agents or combinations of agents against bacteria to serve as a guide for tests in mammals. In this laboratory, candidate anticancer agents are tested singly and in combinations as growth inhibitors for bacteria prior to testing against neoplasms in animals. This report presents some of the data that have been obtained for combinations of agents in tests with bacteria. Methods. To screen for potentiating growth-inhibitory activity, a simple test method was devised using Escherichia coli (ATCC No. 9637) as the test organism. The use of this organism grown in a simple, chemically defined glucose-salts medium is ideal for biochemical studies of this kind because the observed action of specific inhibitors or antimetabolites is not obscured by the presence in the medium of the chemically complex metabolites required in similar studies on more fastidious organisms. Duplicate paper discs saturated with known concentrations of a candidate compound were placed on the surfaces of minimal agar cultures of E. coli in a control plate and in a test plate. The control plate contained no test compound, whereas the test plate contained a subinhibitory concentration of the second member of the pair of candidate compounds being tested for potentiation. If the diameter of the zone of inhibition around the paper disc on the test plate was greater than 2 times that on the control plate, then the combination was considered worthy of further study. Of approximately one thousand pairs of compounds tested, approximately one hundred pairs gave evidence of significant additive or potentiated inhibition.