The semen enhancer of viral infection ( SEVI ) binds bacteria , enhances 1 bacterial phagocytosis by macrophages , and can protect against 2 vaginal infection by a sexually transmitted bacterial pathogen 3 4

25 The semen-derived enhancer of viral infection (SEVI) is a positively charged 26 amyloid fibril that is derived from a self-assembling proteolytic cleavage fragment of 27 prostatic acid phosphatase (PAP248-286). SEVI efficiently facilitates HIV-1 infection in 28 vitro, but its normal physiologic function remains unknown. In light of the fact that other 29 amyloidogenic peptides have been shown to possess direct antibacterial activity, we 30 investigated whether SEVI could inhibit bacterial growth. Neither SEVI fibrils nor the 31 unassembled PAP248-286 peptide had significant direct antibacterial activity in vitro. 32 However, SEVI fibrils bound to both Gram-positive (Staphylococcus aureus) and Gram33 negative (Escherichia coli and Neisseria gonorrhoeae) bacteria, in a charge-dependent 34 fashion. Furthermore, SEVI fibrils but not the monomeric PAP248-286 peptide promoted 35 bacterial aggregation and enhanced the phagocytosis of bacteria by primary human 36 macrophages. SEVI also enhanced binding of bacteria to macrophages and the 37 subsequent release of bacterially-induced pro-inflammatory cytokines (TNFα, IL-6 and 38 IL-1β). Finally, SEVI fibrils inhibited murine vaginal colonization with Neisseria 39 gonorrhoeae. These findings demonstrate that SEVI has indirect antimicrobial activity, 40 and that this activity is dependent on both the cationic charge and the fibrillar nature of 41