Staphylococcus aureus uses the ArlRS and MgrA cascade to regulate immune evasion during skin infection

Cell Rep. 2021 Jul 27;36(4):109462. doi: 10.1016/j.celrep.2021.109462.


Skin is one of the most common sites of host immune response against Staphylococcus aureus infection. Here, through a combination of in vitro assays, mouse models, and intravital imaging, we find that S. aureus immune evasion in skin is controlled by a cascade composed of the ArlRS two-component regulatory system and its downstream effector, MgrA. S. aureus lacking either ArlRS or MgrA is less virulent and unable to form correct abscess structure due to de-repression of a giant surface protein, Ebh. These S. aureus mutants also have decreased expression of immune evasion factors (leukocidins, chemotaxis-inhibitory protein of S. aureus [CHIPS], staphylococcal complement inhibitor [SCIN], and nuclease) and are unable to kill neutrophils, block their chemotaxis, degrade neutrophil extracellular traps, and survive direct neutrophil attack. The combination of disrupted abscess structure and reduced immune evasion factors makes S. aureus susceptible to host defenses. ArlRS and MgrA are therefore the main regulators of S. aureus immune evasion and promising treatment targets.

Keywords: Staphylococcus aureus; abscess; gene regulation; immune evasion; innate immunity; intravital microscopy; neutrophil; skin infection; surface proteins.

Publication types

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

MeSH terms

  • Animals
  • Bacterial Adhesion
  • Bacterial Proteins / metabolism*
  • Cell Death
  • Chemotaxis
  • Extracellular Traps / metabolism
  • Imaging, Three-Dimensional
  • Immune Evasion*
  • Mice, Inbred C57BL
  • Models, Biological
  • Mutation / genetics
  • Neutrophils / metabolism
  • Phagocytosis
  • Reactive Oxygen Species / metabolism
  • Skin / microbiology*
  • Skin / pathology*
  • Staphylococcal Infections / immunology*
  • Staphylococcal Infections / microbiology*
  • Staphylococcus aureus / immunology*
  • Staphylococcus aureus / pathogenicity
  • Virulence
  • alpha-Defensins / metabolism


  • Bacterial Proteins
  • Reactive Oxygen Species
  • alpha-Defensins