Shrimp (Penaeus monodon) anti-lipopolysaccharide factor reduces the lethality of Pseudomonas aeruginosa sepsis in mice

We investigated the efficacy of amino acids 55–76 of the synthetic shrimp anti-lipopolysaccharide factor peptide (SALF55–76 cyclic peptide), the C-terminal part of the shrimp anti-lipopolysaccharide factor. This study was conducted to elucidate the effects of the antiseptic action of this peptide. The SALF55–76 cyclic peptide was tested against bacterial clinical isolates and showed broad-spectrum antimicrobial activity. Transmission electron microscopic (TEM) examination of SALF55–76 cyclic peptide-treated Pseudomonas aeruginosa showed that severe swelling preceded cell death and breakage of the outer membrane; the intracellular inclusion was found to have effluxed extracellularly. When mice were treated with the SALF55–76 cyclic peptide before bacterial challenge with P. aeruginosa, the peptide highly protected mice against death by sepsis. The P. aeruginosa recovered from SALF55–76 cyclic peptide-treated mice after 4 h exhibited reduced bacterial growth similar to that recovered from vancomycin-treated mice. In addition, the syntheses of inflammatory cytokines, such as interleukin (IL)-2, IL-4, IL-10, IL-12, IL-13, interferon-γ, and tumor necrosis factor [TNF]-α, were significantly upregulated 4 h after SALF55–76 cyclic peptide treatment except for IL-4 in the liver. The expressions of Toll-like receptor 4 (Tlr4), Irf3, myd88, and Tram, were considerably elevated, but only Tlr4 existed in the spleen 4 h after SALF55–76 cyclic peptide treatment. The prophylactic administration of SALF55–76 cyclic peptide was begun the TNF-α response in comparison to untreated mice by an ELISA analysis. Due to its multifunctional properties, the SALF55–76 cyclic peptide may become an important prophylaxis against and therapy for bacterial infectious diseases, as well as for septic shock.