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Prophage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes

Stephan Brouwer1, Timothy C Barnett1,2, Diane Ly3,4

  • 1Australian Infectious Diseases Research Centre and School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, Australia.

Nature Communications
|October 7, 2020
PubMed

Insights

Scarlet fever is re-emerging due to Streptococcus pyogenes (GAS) carrying specific phages. These phages produce toxins like SpeC and Spd1, which are crucial for bacterial colonization and virulence.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Pathogenesis

Background:

  • Scarlet fever, caused by Streptococcus pyogenes (group A Streptococcus, GAS), is re-emerging globally.
  • North-East Asian serotype M12 (emm12) GAS strains are linked to scarlet fever outbreaks.
  • Novel prophages, such as ΦHKU.vir, encode virulence factors including superantigens (SSA, SpeC) and DNase (Spd1).

Purpose of the Study:

  • To molecularly characterize the exotoxins encoded by the ΦHKU.vir prophage.
  • To elucidate the role of these exotoxins in Streptococcus pyogenes pathogenesis and virulence.
  • To investigate the synergistic effects of ΦHKU.vir-encoded exotoxins in a host model.

Main Methods:

  • Molecular characterization of ΦHKU.vir-encoded exotoxins.
  • Assessment of streptolysin O (SLO)-induced glutathione efflux.
  • Construction and analysis of isogenic knockout mutants for SSA, SpeC, and Spd1.
  • Evaluation of bacterial colonization in a mouse nasopharyngeal model.

Main Results:

  • Streptolysin O (SLO) induces host glutathione efflux, promoting secreted streptococcal pyrogenic exotoxin A (SSA) release and activity, a novel virulence mechanism.
  • Spd1 is essential for Streptococcus pyogenes resistance to neutrophil killing.
  • SpeC and Spd1 act synergistically to enhance nasopharyngeal colonization in a mouse model.

Conclusions:

  • ΦHKU.vir-encoded exotoxins, including SSA, SpeC, and Spd1, are key contributors to the pathogenesis of scarlet fever-causing GAS.
  • SLO-mediated glutathione efflux represents a new bacterial virulence strategy.
  • Understanding these phage-encoded factors provides insight into scarlet fever's resurgence and GAS virulence.

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