Figure 7. Proposed model of innate immune evasion control by ArlRS and MgrA during S. aureus infection.

With a functional ArlRS-MgrA cascade, the initial signal detected by the ArlRS two-component system induces expression of the global regulator MgrA, which in turn controls expression of various genes involved in virulence and immune evasion. By suppressing expression of large surface proteins with anti-adhesive properties (Ebh and SraP), the active cascade allows S. aureus to bind fibrinogen and form tight three-dimensional abscess communities where bacteria are shielded from phagocytes. Active cascade also causes S. aureus to secrete various immune evasion factors, such a leukocidins (LukAB and LukSF), CHIPS, SCIN, and nuclease, which together act to kill incoming neutrophils, prevent their chemotaxis and movement, and digest NETs used by neutrophils to ensnare bacteria. Finally, due to the cascade’s involvement with S. aureus resistance to antimicrobial peptides and, to a smaller degree, oxygen radicals, active ArlRS and MgrA promote bacterial survival inside neutrophils after phagocytosis. See also Figure S6.