Human SAP Is a Novel Peptidoglycan Recognition Protein That Induces Complement-Independent Phagocytosis of Staphylococcus aureus

Abstract

The human pathogen Staphylococcus aureus is responsible for many community-acquired and hospital-associated infections and is associated with high mortality. Concern over the emergence of multidrug-resistant strains has renewed interest in the elucidation of host mechanisms that defend against S. aureus infection. We recently demonstrated that human serum mannose-binding lectin (MBL) binds to S. aureus wall teichoic acid (WTA), a cell wall glycopolymer, a discovery that prompted further screening to identify additional serum proteins that recognize S. aureus cell wall components. In this report, we incubated human serum with 10 different S. aureus mutants and determined that serum amyloid P component (SAP) bound specifically to a WTA-deficient S. aureus ΔtagO mutant, but not to tagO-complemented, WTA-expressing cells. Biochemical characterization revealed that SAP recognizes bacterial peptidoglycan as a ligand and that WTA inhibits this interaction. Although SAP binding to peptidoglycan was not observed to induce complement activation, SAP-bound ΔtagO cells were phagocytosed by human polymorphonuclear leukocytes in an Fcγ receptor-dependent manner. These results indicate that SAP functions as a host defense factor, similar to other peptidoglycan recognition proteins and nucleotide-binding oligomerization domain (NOD)-like receptors.

CCN1 is an opsonin for bacterial clearance and a direct activator of Toll-like receptor signaling

“…Opsonins are structurally diverse frontline defense molecules that recognize and bind bacteria to mark them for phagocytosis and elimination through specific cell surface receptors 52 . Families of opsonins include antibodies, complement proteins, and factors such as pentraxins (serum amyloid P and Creactive protein) 53,54 , collectins 55 , and ficolins 56 . As each opsonin may have idiosyncratic target specificities and efficacy, the nature and availability of specific opsonins at the sites of infection may affect the pathological outcome.…”

Functional characterisation and expression analysis of recombinant serum amyloid P isoform 1 (RbSAP1) from rock bream (Oplegnathus fasciatus)

“…Nevertheless, the binding and agglutination of Gram-positive bacteria was relatively low. Recent studies have also shown that wall teichoic acid prevents the binding of SAP to PGN [50]. Interestingly, SAP enhances the antibacterial activity of mouse macrophages toward Listeria monocytogenes (a Gram-positive species), and this activity is not associated with the binding of SAP to the pathogen [51].…”

Bacteria under stress by complement and coagulation

“…CRP interacts with phosphocholine (PC) that is present in a number of bacterial structures including the teichoic acid of S. pneumoniae (Volanakis, ). SAP binds a variety of bacterial cell wall structures such as carbohydrates, LPS, and peptidoglycan (Hind et al ., ; Noursadeghi et al ., ; An et al ., ). Alternatively, C1q can bind directly to the bacterial surface to activate the CP.…”