Studies on Resistance to Antibiotics

The discovery of gramicidin, penicillin, streptomycin, and the numerous other antibiotics known today has contributed materially to the list of therapeutic agents available against micro-organisms. However, the immediate enthusiasm which greeted their introduction has had to be checked by the realization that many of the important organisms affected readily develop resistance to the antibiotic agents, just as they have to the sulfonamides. Further knowledge of the mechanisms by which organisms acquire such resistances may be fundamental to our understanding of the mechanism of action of the antibiotic. On the practical side, too, there is the possibility, remote as it may be, that insight into the problem might enable effective countermeasures to be instituted. Our kn,owledge of the rOle of individual enzymes in metabolism is due in part to the experimental use of inhibiting substances which block these catalysts more or less specifically. The effect of loss of a given enzyme on a particular system can thus be ascertained and its contribution to the total metabolism evaluated. In approaching the problem of the natural and acquired resistance of micro-organisms to penicillin we have been interested in the possible rOle of a known agent for destroying penicillin-penicillinase. This enzyme (or -enzymes) has -been demonstrated to be present in some but by no means all bacteria. Although there is definite