Hiding in plain sight: immune evasion by the staphylococcal protein SdrE

Abstract

The human immune system is responsible for identification and destruction of invader cells, such as the bacterial pathogen In response, brings to the fight a large number of virulence factors, including several that allow it to evade the host immune response. The staphylococcal surface protein SdrE was recently reported to bind to complement Factor H, an important regulator of complement activation. Factor H attaches to the surface of host cells to inhibit complement activation and amplification, preventing the destruction of the host cell. SdrE binding to Factor H allows to mimic a host cell and reduces bacterial killing by granulocytes. In a new study published in, Zhang et al. describe crystal structures of SdrE and its complex with the C-terminal portion of Factor H. The structure of SdrE and its interaction with the Factor H peptide closely resemble a family of surface proteins that recognize extracellular matrix components such as fibrinogen. However, unbound SdrE forms a novel 'Closed' conformation with an occluded peptide-binding groove. These structures reveal a fascinating mechanism for immune evasion and provide a potential avenue for the development of novel antimicrobial agents to target SdrE.

Staphylococcus aureusST228 and ST239 as models for expression studies of diverse markers during osteoblast infection and persistence

“…In the process of adhesion, cell surface proteins (adhesins) of the Microbial Surface Component Recognizing Adhesive Matrix Molecules (MSCRAMM) play an important role in the pathogenesis of osteoarticular infections (OM and PJIs). Among these, an important role is played by: the fibronectin‐binding proteins A and B (FnbA/B); the fibrinogen‐binding protein clumping factors A and B (ClfA/B); the bone sialoprotein binding protein (Bbp); the collagen adhesin (CNA) (Otsuka et al, 2006; Pérez‐Montarelo et al, 2018); and SdrE, a serine–aspartate (SD) protein that anchors the cell wall interacting with complement factor H and facilitates colonization through adherence to the cell surface or extracellular matrix (ECM) components (Herr & Thorman, 2017).…”

Staphylococcus aureus ST228 and ST239 as models for expression studies of diverse markers during osteoblast infection and persistence

“…In the process of adhesion, cell surface proteins (adhesins) of the Microbial Surface Component Recognizing Adhesive Matrix Molecules (MSCRAMM), play an important role in the pathogenesis of osteoarticular (OM and PJ) infections. Among these, fibronectin binding proteins A and B (FnbA/B), fibrinogen-binding protein clumping factors A and B (ClfA/B), the bone sialoprotein binding protein (Bbp), the collagen-adhesin (CNA) (Perez-Montarelo et al, 2018;Otsukaet al , 2006) and SdrE, a serine-aspartate (SD) protein that anchors the cell-wall interacting with complement Factor H and facilitates colonization through adherence to the cell surface or extracellular matrix (ECM) components (Herr and Thorman, 2017).…”

Adhesive Virulence Factors of Staphylococcus aureus Resist Digestion by Coagulation Proteases Thrombin and Plasmin

“…SdrD was noteworthy as an adhesin that was highly resistant toward digestion (Tables , , and ) and yet has no known blood borne binding partners. Its only known partner is the keratinocyte surface protein desmoglein 1, , promoting S. aureus nasal colonization (Table ). Recent work showed that the expression of SdrD improved survival of Lactococcus lactis in human blood, possibly by inducing killing of neutrophils, implying that SdrD does have one or several more binding partners in blood to be identified …”