Antigenic Relationships Between M, S, and R Phases of Streptococci and Their Diphtheroid Descendants
Authors: Mellon Ralph R. 
Published: January 2023

Summary and Conclusions
An S phase culture of a Group A, Type 4, hemolytic streptococcus, isolated from a case of cellulitis, has been observed to undergo repeated spontaneous transformation to a typical non-hemolytic diphtheroid. The latter maintained a definite degree of antigenic community with the parental streptococcus, which was not the case for other Group A streptococci against which it was tested. A series of intermediate culture phases between the hemolytic streptococcus and the non-hemolytic diphtheroid has been dissociated. These comprise the M, R, and midget-diphtheroid, etc. With their aid it has been possible to reinforce the evidence for an antigenic continuity between these two genera, heretofore conspicuously absent. Fragments of the complete antigenic mosaic may be thought of as being distributed among the several cultural phases. This antigenic fragmentation finds expression in the lack of full agglutinogenic reciprocity between the phases, as indicated by the major-minor agglutinative reaction. The antigenic pattern of Group A hemolytic streptococci has been observed to undergo varying degrees of reconstitution following redissociation of the R and diphtheroid intermediates to the parent S phase of the streptococcus. The change is in the direction of increased antigenic complexity; thus, a type-specific streptococcus developed antigenic resemblances to most of the other thirteen types of Group A with which it was compared. Furthermore, the diphtheroid-derived from a Group A streptococcus has been shown to be associated with such a far-reaching reconstitution of the antigenic and cultural patterns that, on its redissociation to a hemolytic streptococcus, a Group C animal type resulted. From the standpoint of variability, this study has effected a reconciliation between the dissociative process per se, whose culture phases are usually related antigenically, and the pleobiotic process whose end-stages are usually distinct in this respect. The differentiative process underlying both phenomena appears as a continuous one, there being no evidence that it is essentially different in either. That such far-reaching cultural and antigenic reconstitutions as those resulting from pleobiosis should so often have coccoidal spore-like gonidia as their seat of change, supports our traditional interpretation of their function as “embryonic reorganization forms.” By the same token their evaluation as “involution forms” in the sense in which the term has been conventionally employed by monomorphic theory, can be dismissed. Actually the involution that they undergo is often but a prelude to the evolution that they are capable of displaying. The correlation between the cultural and antigenic reconstitutions implemented by these pleomorphic asexual cells is essentially dynamic. Thus, the antigenic and/or virulence-characters attained under a diphtheroidal imprimatur may be indefinitely retained after such morphology has disappeared. When such pleomorphic changes reflect the re-creation of functional individuality of the parental vegetative phase, what is achieved is quite in line with changes incident to reproductive cells. From the epidemiological standpoint, this study is suggestive in several directions. The exaltation of virulence usually associated with redissociation of the streptococcus from its R and diphtheroid stages, especially when it is coupled with increase in antigenic complexity, presents a new point of view, we believe on the origin of epidemic types. The reintegration of virulence into a cultural pattern so transformed that a change of host results, is the first clear experimental evidence showing a variational sequence mechanism whereby an animal parasite may become adapted to man and vice versa. The study also has reverberations into the “carrier” situation. The possibility that in nature or in the living host there might exist evolutionary stages in the life-history of a parasite that are so far removed taxonomically as to be virtually unrecognizable, has not received the definitive sort of experimental support described here, so far as we know. Whether we regard the reversible changes between micro-organisms to be of true cyclic origin, or to mutation, or both, is not likely to make vital differences to applied bacteriology. However, when applied to such important considerations as resistance to chemotherapeutic agents, the cyclic role of a gonidial reproductive phase may not be as academic as has been assumed.