Semen-Derived Enhancer of Viral Infection (SEVI) Binds Bacteria, Enhances Bacterial Phagocytosis by Macrophages, and Can Protect against Vaginal Infection by a Sexually Transmitted Bacterial Pathogen

The semen-derived enhancer of viral infection (SEVI) is a positively charged amyloid fibril that is derived from a self-assembling proteolytic cleavage fragment of prostatic acid phosphatase (PAP248-286). SEVI efficiently facilitates HIV-1 infection in vitro, but its normal physiologic function remains unknown. In light of the fact that other amyloidogenic peptides have been shown to possess direct antibacterial activity, we investigated whether SEVI could inhibit bacterial growth. Neither SEVI fibrils nor the unassembled PAP248-286 peptide had significant direct antibacterial activity in vitro. However, SEVI fibrils bound to both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli and Neisseria gonorrhoeae) bacteria, in a charge-depen-dent fashion. Furthermore, SEVI fibrils but not the monomeric PAP248-286 peptide promoted bacterial aggregation and enhanced the phagocytosis of bacteria by primary humanmacrophages. SEVI also enhanced binding of bacteria to macrophages and the subsequent release of bacterially induced proinflammatory cytokines (tumor necrosis factor alpha [TNF-], interleukin-6 [IL-6], and IL-1). Finally, SEVI fibrils inhibited murine vaginal colonization withNeisseria gonorrhoeae. These findings demonstrate that SEVI has indirect antimicrobial activity and that this activity is dependent on both the cationic charge and the fibrillar na-ture of SEVI. Human semen has recently been shown to contain cationicamyloid fibrils (1–3), the best characterized of which is the semen-derived enhancer of viral infection (SEVI) (3). SEVI is formed from a self-assembling peptide cleavage product of pros