title: 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.
abstract: 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 (PAP(248-286)). 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 PAP(248-286) 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-dependent fashion. Furthermore, SEVI fibrils but not the monomeric PAP(248-286) peptide promoted bacterial aggregation and enhanced the phagocytosis of bacteria by primary human macrophages. SEVI also enhanced binding of bacteria to macrophages and the subsequent release of bacterially induced proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6], and IL-1β). Finally, SEVI fibrils inhibited murine vaginal colonization with Neisseria gonorrhoeae. These findings demonstrate that SEVI has indirect antimicrobial activity and that this activity is dependent on both the cationic charge and the fibrillar nature of SEVI.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: David
authors.initials: D
authors.lastname: Easterhoff
authors.forename: Fernando
authors.initials: F
authors.lastname: Ontiveros
authors.forename: Lauren R
authors.initials: LR
authors.lastname: Brooks
authors.forename: Yoel
authors.initials: Y
authors.lastname: Kim
authors.forename: Brittany
authors.initials: B
authors.lastname: Ross
authors.forename: Jharon N
authors.initials: JN
authors.lastname: Silva
authors.forename: Joanna S
authors.initials: JS
authors.lastname: Olsen
authors.forename: Changyong
authors.initials: C
authors.lastname: Feng
authors.forename: Dwight J
authors.initials: DJ
authors.lastname: Hardy
authors.forename: Paul M
authors.initials: PM
authors.lastname: Dunman
authors.forename: Stephen
authors.initials: S
authors.lastname: Dewhurst
mesh_terms: D000135:Acid Phosphatase; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D009344:Neisseria gonorrhoeae / Q000187:drug effects; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects*; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry* / Q000378:metabolism; D012661:Semen / Q000737:chemistry* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism; D016585:Vaginosis, Bacterial / Q000517:prevention & control*
chemical_list: D000682:Amyloid; D000900:Anti-Bacterial Agents; D016207:Cytokines; D010446:Peptide Fragments; D000135:Acid Phosphatase; C428439:prostatic acid phosphatase; D017027:Protein Tyrosine Phosphatases