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Group A Streptococcal M1 Protein Provides Resistance against the Antimicrobial Activity of Histones.

  • Author(s): Döhrmann, Simon;
  • LaRock, Christopher N;
  • Anderson, Ericka L;
  • Cole, Jason N;
  • Ryali, Brinda;
  • Stewart, Chelsea;
  • Nonejuie, Poochit;
  • Pogliano, Joe;
  • Corriden, Ross;
  • Ghosh, Partho;
  • Nizet, Victor
  • et al.

Published Web Location

https://doi.org/10.1038/srep43039
Abstract

Histones are essential elements of chromatin structure and gene regulation in eukaryotes. An unexpected attribute of these nuclear proteins is their antimicrobial activity. A framework for histone release and function in host defense in vivo was revealed with the discovery of neutrophil extracellular traps, a specialized cell death process in which DNA-based structures containing histones are extruded to ensnare and kill bacteria. Investigating the susceptibility of various Gram-positive pathogens to histones, we found high-level resistance by one leading human pathogen, group A Streptococcus (GAS). A screen of isogenic mutants revealed that the highly surface-expressed M1 protein, a classical GAS virulence factor, was required for high-level histone resistance. Biochemical and microscopic analyses revealed that the N-terminal domain of M1 protein binds and inactivates histones before they reach their cell wall target of action. This finding illustrates a new pathogenic function for this classic GAS virulence factor, and highlights a potential innate immune evasion strategy that may be employed by other bacterial pathogens.

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