Figure 6. Proposed mechanism of action for the histone sensing system in MSSA and MRSA.

(A) In planktonic cells, histones bind to the anionic loop of ApsS and trigger the activation of the apsS and apsR genes encoding the sensor and regulator proteins of aps system. This leads to the activation of the aps controlled resistance mechanism mediated through vraFG transporter genes involved in either exporting the pore forming histones or importing them for proteolytic inactivation. (B) In biofilms embedded cells, histone binding to the anionic loop of ApsS leads to the induction of the dltB gene encoding dlt operon involved in D- alanylation of teichoic acids, in addition to the vraF gene involved in peptide transport.