Serum Amyloid A Protein Binds to Outer Membrane Protein A of Gram-negative Bacteria

Abstract

Serum amyloid A (SAA) is the major acute phase protein in man and most mammals. We observed SAA binding to a surprisingly large number of Gram-negative bacteria, including Escherichia coli, Salmonella typhimurium, Shigella flexneri, Klebsiella pneumoniae, Vibrio cholerae, and Pseudomonas aeruginosa. The binding was found to be high affinity and rapid. Importantly, this binding was not inhibited by high density lipoprotein with which SAA is normally complexed in serum. Binding was also observed when bacteria were offered serum containing SAA. Ligand blots following SDS-PAGE or two-dimensional gels revealed two major ligands of 29 and 35 kDa that bound SAA when probing with radiolabeled SAA or SAA and monoclonal anti-SAA. Following fractionation the ligand was found in the outer membrane fraction of E. coli and was identified by matrix-assisted laser desorption ionization time-offlight mass spectrometry to be outer membrane protein A (OmpA). OmpA-deficient E. coli did not bind SAA, and following purification of OmpA the protein retained binding activity. The ligands on other bacteria were likely to be homologues of OmpA because wild type, but not OprF-deficient, P. aeruginosa bound SAA.

Acute phase response in Chinese soft-shelled turtle (Trionyx sinensis) with Aeromonas hydrophila infection

“…TLR activation recruits several downstream factors regulating the expression of immune relevant genes (such as pro-inflammatory cytokine genes). The pattern recognition functions of SAA have also been identified with binding to a range of Gram-negative bacteria (Hari-Dass et al, 2005). Thereby, SAA up-regulation observed in this study may contribute to the establishment of an efficient reptilian immune response and TLR signaling pathway, and serve as a main APP and biomarker of infection, especially at the early stage, in reptiles.…”

Pathogenic Serum Amyloid A 1.1 Shows a Long Oligomer-rich Fibrillation Lag Phase Contrary to the Highly Amyloidogenic Non-pathogenic SAA2.2

“…Thus, the structural malleability of SAA1.1 and SAA2.2 we observed in vitro may reflect the in vivo properties of SAA proteins to allow the regulation of their many putative functions related to cholesterol metabolism and the inflammatory responses (34). Furthermore, it would help explain how a small (103-104 residues) and marginally stable protein like SAA is able to interact in vivo with many binding partners, including HDL, cholesterol (37), outer membrane protein (38), heparin (39), extracellular matrix glycoproteins (40), and platelets (41).…”

Serum amyloid A has antiviral activity against hepatitis C virus by inhibiting virus entry in a cell culture system

“…Indeed, SAA has been shown to bind to the outer membrane protein A of a large number of Gram-negative bacteria and to be involved in opsonization of these bacteria. 32,33 The observations that SAA binds to HCV and has an antiviral activity against this virus provide experimental evidence that SAA can have a direct effect against pathogens. This observation is in favor of a role for SAA in the innate immune response against HCV.…”