espite possessing similar virulence determinants, group G beta-hemolytic streptococci (GGS) are less virulent than group A streptococci (GAS), tending to cause infection in patients with comorbidities. The sil locus in GAS encodes the quorum-sensing peptide SilCR, which attenuates infection in a mouse model of necrotizing fasciitis. Michael-Gayego et al. (p. 4121–4127) find that the sil locus is much more prevalent in GGS than in GAS. SilCR is expressed on the bacterial surface and secreted. Challenge of SilCR-immunized mice with GGS results in significantly more severe infection than in nonimmunized mice, suggesting that protective immunity may be a double-edged sword.