Staphylococcus aureus Phenol-Soluble Modulins α1-α3 Act as Novel Toll-Like Receptor (TLR) 4 Antagonists to Inhibit HMGB1/TLR4/NF-κB Signaling Pathway.

ABSTRACT: Phenol-soluble modulins (PSMs) have recently emerged as key virulence determinants, particularly in highly aggressive Staphylococcus aureus isolates. These peptides contribute to the pathogenesis of S. aureus infections, participating in multiple inflammatory responses. Here, we report a new role for S. aureus PSMs in high mobility group box-1 protein (HMGB1) induced inflammation by modulating toll-like receptor (TLR) 4 pathway. Direct ligation of TLR4 with S. aureus PSMα1-α3 and PSMβ1-β2 was identified by surface plasmon resonance. Remarkably, the binding affinity of TLR4 with HMGB1 was attenuated by PSMα1-α3. Further study revealed that PSMα1-α3 directly inhibited HMGB1-induced NF-κB activation and proinflammatory cytokines production in vitro using HEK

SUBMITTER: Chu M 

PROVIDER: S-EPMC5996891 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature