Abstract
Serum amyloid A (SAA), one of the major highly conserved acute-phase proteins in most mammals, is predominantly produced by hepatocytes and also by a variety of cells in extrahepatic tissues. It is well-known that the expression of SAA is sharply increased in bacterial infections. However, the exact physiological function of SAA during bacterial infection remains unclear. Herein, we showed that SAA expression significantly increased in abscesses of Staphylococcus aureus cutaneous infected mice, which exert direct antibacterial effects by binding to the bacterial cell surface and disrupting the cell membrane in acidic conditions. Mechanically, SAA disrupts anionic liposomes by spontaneously forming small vesicles or micelles under acidic conditions. Especially, the N-terminal region of SAA is necessary for membrane disruption and bactericidal activity. Furthermore, we found that mice deficient in SAA1/2 were more susceptible to infection by S. aureus In addition, the expression of SAA in infected skin was regulated by interleukin-6. Taken together, these findings support a key role of the SAA in host defense and may provide a novel therapeutic strategy for cutaneous bacterial infection.
Highlights
Serum amyloid A (SAA) is a major acute phase protein and highly conserved from sea cucumber to human
We first evaluated the expressions of SAA1/2/3 in an S. aureus cutaneous infected mouse model and found that mRNA levels of SAAs were significantly increased both in the skin and liver of the infected mice (Fig. 1A and Fig. S1)
To investigate whether SAA has a direct bactericidal effect, we tested the activity of SAA against E. coli and S. aureus, which are representatives for Gram-negative and the purified recombinant mSAA1 to E. coli and S. aureus at acidic pH were strongly enhanced (Fig. 2A and B)
Summary
Serum amyloid A (SAA) is a major acute phase protein and highly conserved from sea cucumber to human. We showed that SAA expressed significantly increased in abscesses of Staphylococcus aureus (S. aureus) cutaneous infected mice, which exert direct antibacterial effects by binding to the bacterial cell surface and disrupting the cell membrane at acidic condition.
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