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

Easterhoff D,Ontiveros F,Brooks LR,Kim Y,Ross B,Silva JN,Olsen JS,Feng C,Hardy DJ,Dunman PM,Dewhurst S

doi

10.1128/AAC.02464-12

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

2443-50

issue

6

eissn

0066-4804

issn

1098-6596

pii

AAC.02464-12

journal_volume

57

pub_type

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