Abstract
Streptococcus pyogenes (group A Streptococcus) is a globally disseminated and human-adapted bacterial pathogen that causes a wide range of infections, including scarlet fever. Scarlet fever is a toxin-mediated disease characterized by the formation of an erythematous, sandpaper-like rash that typically occurs in children aged 5 to 15. This infectious disease is caused by toxins called superantigens, a family of highly potent immunomodulators. Although scarlet fever had largely declined in both prevalence and severity since the late 19th century, outbreaks have now reemerged in multiple geographical regions over the past decade. Here, we review recent findings that address the role of superantigens in promoting a fitness advantage for S. pyogenes within human populations and discuss how superantigens may be suitable targets for vaccination strategies.
Highlights
Scarlet fever is a disease of historic significance, described as early as around 400 BC by Hippocrates, and reports during the premodern period (1,500 to 1,900 CE) often describe scarlet fever epidemics with very high mortality rates [3]
The majority of scarlet fever-associated lineages contained the unifying characteristic of 2 important mobile genetic elements: toxin-harboring prophages encoding streptococcal superantigens SSA and SpeC, and the DNase Spd1 (e.g., FHKU.vir), and integrative and conjugative elements (ICEs) encoding multidrug resistance to tetracycline and macrolides (e.g., ICE-emm12) [9,12]
Though the apparent redundancy of S. pyogenes superantigens has not been entirely explained, antigenic diversity within this toxin family [17] may allow for superantigens to both escape humoral immunity [18] and to recognize an assorted range of TCR β-chains and MHC-II, thereby subverting initiation of adaptive immune responses (Fig 1)
Summary
Citation: Hurst JR, Brouwer S, Walker MJ, McCormick JK (2021) Streptococcal superantigens and the return of scarlet fever. PLoS Pathog 17(12): e1010097. https://doi.org/10.1371/journal. ppat.1010097 Funding: This work was supported by grants from the Canadian Institutes of Health Research to JKM and the National Health and Medical Research Council of Australia to MJW. JH was supported in part by a Queen Elizabeth II Graduate Scholarship in Science and Technology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
