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

Sci Rep. 2017 Feb 21:7:43039. doi: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Bacterial / metabolism
  • Antigens, Bacterial / physiology*
  • Bacterial Outer Membrane Proteins / metabolism
  • Bacterial Outer Membrane Proteins / physiology*
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Histones / metabolism*
  • Humans
  • Immune Evasion*
  • Neutrophils / immunology*
  • Neutrophils / metabolism
  • Streptococcal Infections / metabolism
  • Streptococcal Infections / microbiology*
  • Streptococcus pyogenes / metabolism
  • Streptococcus pyogenes / pathogenicity
  • Streptococcus pyogenes / physiology*
  • Virulence Factors / metabolism
  • Virulence Factors / physiology

Substances

  • Antigens, Bacterial
  • Bacterial Outer Membrane Proteins
  • Carrier Proteins
  • Histones
  • Virulence Factors
  • streptococcal M protein