The Role of Temperate Bacteriophage in the Production of Erythrogenic Toxin by Group a Streptococci

Abstract

In 1927 Frobisher and Brown (1) using doubly marked bacterial strains demonstrated that a filtrable agent isolated from scarlatinal strains of hemolytic streptococci could induce the formation of erythrogenic toxin by non-scarlatinal strains. This newly formed extracellular product was neutralized by standard antitoxins, and the capacity to produce erythrogenic toxin was carried through several subcultures. Bingel (2) essentially confirmed these findings, but the isolation of the filtrable agent responsible for the acquisition of this new property by non-toxin-producing strains was not reported in either of these studies. In view of the current knowledge of bacteriophages these earlier preliminary observations suggested that a streptococcal bacteriophage might play a role in the production of erythrogenic toxin.This hypothesis was further strengthened by the series of classic papers published by Freeman (3,4). He demonstrated that avirulent strains could be rendered both t0xinogenic and lysogenic following exposure to bacteriophages obtained from virulent strains of Corynebacteriura diphtheriae. The toxigenicity could be carried through many bacterial generations and did not depend on chance phage contamination of the organism. Freeman (4), therefore, concluded that an important relationship existed between the lysogenic state of the organism and its toxigenicity and suggested that the mechanism of the effect might be either mutant selection or an induced change in the bacterial metabolism as a result of lysogenization of the bacterial strain. These remarkable observations have been subsequently confirmed by Groman (5), Barksdale et al. (6), and Parsons (7), and the evidence now indicates that this property is indeed a cellular change under the genetic control of the phage.It is known from the recent work of Kranse (8) and Kjems (9) that lysogeny is quite common in Group A hemolytic streptococci, and this finding strengthened the possibility that the transmissible toxigenicity observed by Frobisher and Brown might depend on a relationship between streptococci and lysogenic bacteriophages similar to that described in the C. diphtheria lysogenic complex.

Induction of Lysogenic Bacteriophage and Phage-Associated Toxin from Group A Streptococci during Coculture with Human Pharyngeal Cells

“…The literature is replete with examples of bacteriophage-encoded toxin upregulation resulting from bacteriophage induction (8,11,13); however, such phage induction is usually the result of wholly artificial and nonspecific conditions (e.g., UV irradiation or mitomycin C). Although bacteriophage induction resulting from the bacterial interaction with the host cell environment has not been previously reported, we speculated that in the presence of pharyngeal cells, the observed upregulation of SpeC may occur as a result of bacteriophage induction.…”

“…Many pathogenic bacteria are lysogenized, often with more than one lysogen, as observed in streptococci and staphylococci; however, except for the production of toxins in some systems (8,11,13), the role that these lysogens play in pathogenesis is unknown. Our findings may, for the first time, offer insight into the fundamental relationship between bacteria and their prophage.…”

Functional Characterization of Streptococcal Pyrogenic Exotoxin J, a Novel Superantigen

“…The extensive homology among streptococcal and staphylococcal superantigens suggests that they share a common ancestor, either before the evolutionary divergence of the two organisms or as a result of horizontal gene transfer. The two prototypic streptococcal superantigens, SPE A and SPE C, are both encoded on functional phage (11, 20-23, 26, 39, 41), and lateral movement by converting bacteriophage has been demonstrated for both speA (19,63,65) and speC (11). Comparison of the phylogenetic tree constructed from all known streptococcal and staphylococcal bacterial superantigens reveals three main evolutionary branches, not including SPE H (Fig.…”

Studies on Streptococcal Bacteriophages

“…Stock lysates of phages T253 (T12gl), T253 (B940), and T25a (B276) were obtained by the following method. Isolation of temperate phage from lysogenic streptococcal strains were obtained as previously described (3). The plaques obtained by this method were picked by repeated stabbings of the plaque centers and transfer of the adhering virus particles to 5 ml of dialysate broth.…”