The Polyphasic Potencies of the Bacterial Cell; Its General Biologic and Chemotherapeutic Significance

Abstract

The experimental data of this communication really represent the fourth paper in a series dealing with the effects of the sulfonamide drugs on certain pathogenic bacteria as inifluenced by variability. The first three papers have already appeared. Mellon, 1941) (Hadley and and (Hadley, Hadley, and Leathen, 1941). The pattern of bacterial variability associated with the action of these drugs in vivo has had no clear recognition heretofore; but, by way of anticipation, a clue to its nature is afforded by a certain similarity with what have sometimes been referred to as "environmental modifications."These latter have never-been considered as true bacterial variants, or even as playing any r6le in the variation process, for two rather specious reasons. The first of these concerns their lack of stability; and the second, the misconception that they were merely morphologic alterations and therefore of no importance.In the first paper of the series we demonstrated that the erroneously styled series of involution forms of the pneumococcus occurring in vivo under the impact of sulfanilamide action, were actually phasic entities. This fact was considered of transcendent importance too, because the gradient of disappearing virulence which the several phases represented, made them vulnerable to destruction by the immunologic forces of the host. The proof of our contention as to the essentially phasic nature of the pleomorphic cell-forms, was made possible by their isolation in culture where their biochemical and colonial differences became measurable.It is our belief that the pattern of variability shown in the pneumococcus, while in itself distinctive, is not in principle a specific effect of the action of the sulfonamide compounds. In fact, the variability phenomena of the organism we are now about to describe have not been evoked by the action of these drugs; and yet the principles involved do not seem to differ and even the phenomena themselves have much in common. On the other hand, the latter are so much more inclusive that a unique opportunity is provided for the integration and clarification of relationships that have long been in dispute. This is due in part to the fact that it is unusual to encounter a single organism possessing such a range of variability as this one did.Incidentally, the intimate bearing of such considerations on the mode of action of the drugs that have made a new epoch in the history of medicine, should make 1 on August 4, 2020 by guest

Antigenic modulation ofBordetella pertussis

“…It was introduced by Weiss (Bloom, 1937) to denote reversible changes of appearance and behaviour shown by tissue cells under different environmental conditions. It has since been used with much the same sense for changes in metazoon cells by Weiss (1939Weiss ( , 1947Weiss ( , 1949Weiss ( , 1953, Waddington (1948) and Fell (1954), for enzymic adaptation (induced enzyme activity) in bacteria by Monod (1947) and Waddington (1953) and in a somewhat similar sense by Mellon & Hagan (1942) and Hinshelwood (1957). Schmitt (1956) has employed it recently for the effects of specific substances on the reversible interaction of DNA and protein macromolecules, Zuckerman (1957) for environmentally induced changes in pituitary and re-productive activity, and Brodie & Hogben (1957) for the reversible action of drugs on enzyme systems.…”

Conditions Contributing to Streptococcal Virulence

“…It might be anticipated, moreover, that the same sort of problem exists for physiological attributes other than virulence.4 These might include those attributes of bacteria that underlie susceptibility or resistance to drugs, germicides and the various humoral or cellular mechanisms of defense in the animal host. It is probable that some of the variants concerned are related to the new catagory of variability recently proposed by Mellon (1942) with special reference to the probable mode of action of the sulfonamide drugs in vivo on pneumococci; also with relation to some other phenomena of bacterial variability. It is still too early to reach a conclusion regarding the relation of the"modulations" of Mellon to the intra-phasic variations in virulence reported in this paper.…”