PMC

Phylogeny of zeta toxin (PezT) (A) and epsilon antitoxin (PezA) (B) protein sequences. Eighty-eight zeta toxin protein sequences (A) and seventy-two epsilon antitoxin protein sequences (B) from Streptococcus, Enterococcus, Oribacterium, Veillonella and Gardnerella bacterial species were aligned. The genetic relationships were determined as detailed in Figure  .

Classification of TAS. (A) Type I TAS. Several genetic organizations of this type have been reported (, ), and one of the examples is shown here: the two genes encoding the antitoxin and the toxin are organized in opposite orientations, and they are transcribed individually from their own promoters. The antitoxin is an antisense mRNA which prevents the translation of the toxin (a protein). (B) Type II (proteic) TAS. Both TA genes are arranged as an operon, with the antitoxin gene usually preceding the toxin gene. The two genes encoding the TAS are cotranscribed as a single mRNA transcript from the promoter(s), which is placed upstream of the antitoxin gene and subsequently translated. The antitoxins counteract the toxic effect of the cognate toxins by binding avidly to the toxin protein, thus neutralizing the toxic effect. (C) Type III TAS. The organization of both TA genes is the same as that of type II TAS, but instead of protein-protein interactions, the toxin protein is inactivated by the antitoxin mRNA. Green indicates the antitoxin components, whereas beige indicates the toxin components.

Genetic organization of novel putative pneumococcal TAS found in this study. (A) Three-component Xre-COG2856CA TAS. The gene for the COG2856C toxin is located upstream of the COG2856A toxin gene, with both toxins possibly sharing a common Xre antitoxin. The xre reading frame overlapped the upstream portion of the COG2856C reading frame. (B to D) For Xre-COG2856B, besides the typical gene organization in which the Xre antitoxin precedes the COG2856B toxin, relBE2 (B), a Zn-peptidase (C), as well as a Zn-peptidase and an unknown gene (D) are found between Xre and COG2856B. (E) For the putative Xre-Bro TAS family, two contrasting gene organizations were evident: the xre antitoxin gene preceded the Bro1 toxin gene, whereas the Bro2 toxin gene preceded the xre antitoxin gene.

Prevalence of patients having high antitoxin IgM antibodies against superantigens. Open and closed circles, open and closed squares, and open and closed triangles indicate staphylococcal enterotoxin A, staphylococcal enterotoxin B, staphylococcal enterotoxin C, toxic shock syndrome toxin-1, streptococcal pyrogenic exotoxin A, and any of the 5 superantigens, respectively.