Prevention of Death in Bacterium-Infected Mice by a Synthetic Antimicrobial Peptide, L5, through Activation of Host Immunity

Abstract

In our previous study, we found that the antibacterial peptide KLKLLLLLKLK-NH 2 (L5) and its denantiomer (DL5) activate neutrophils to produce superoxide anions (O 2 ؊ ) and prevent death due to infection by methicillin-resistant Staphylococcus aureus, suggesting that these peptides may elicit in vivo antimicrobial activities through host inflammatory responses mediated by neutrophils. In this study, we investigated the mechanisms behind in vivo antimicrobial prophylaxis by the use of L5 for the treatment of bacterial infection introduced via intra-abdominal implantation. We found that the intraperitoneal treatment with L5 before bacterial infection markedly reduced rates of death due to infection. Treatments with L5 were highly effective in preventing death due to intraperitoneal inoculation of not only S. aureus Smith but also Enterococcus faecalis SR1004 and Escherichia coli EC14. The intra-abdominal administration of L5 induced accumulation of neutrophils, increased levels of reactive oxygen species, and augmented antibacterial activity in the abdominal cavity. In addition, administration of L5 upregulated the expression of the Mig/CXCL9 chemokine gene in thioglycolate-elicited peritoneal macrophages. Our results suggested that the prevention of death by treatment of infected mice with L5 might occur primarily through the activation of a host immune response.

D-form KLKLLLLLKLK-NH2 peptide exerts higher antimicrobial properties than its L-form counterpart via an association with bacterial cell wall components

“…The undecapeptide KLKLLLLLKLK-NH 2 was developed by modifying the primary structure of RSLCLLHCRLK-NH 2 . In addition to its activity against Gram-positive bacteria, Gram-negative bacteria, and fungi 18 , KLKLLLLLKLK-NH 2 has been shown to enhance mammalian immune responses via undefined molecular mechanisms 19 20 21 . The antimicrobial activity of the D-form KLKLLLLLKLK-NH 2 , which was synthesized using D-amino acids, persisted longer than the L-form because of its resistance to proteolytic degradation 18 .…”

New Molecular Strategies for Reducing Implantable Medical Devices Associated Infections

“…Even though molecular mechanisms involved in this phenotype are not known, it was demonstrated that the synthetic peptides stimulate host immunity and modulate bacteria virulence by interfering with core QS signaling pathways [53]. Even though synthetic peptides demonstrated a great efficiency in many local difficult to treat infections in vitro and in vivo, such as oral mucositis associated with chemotherapy, diabetic ulcers, chronic lung infections associated with cystic fibrosis, and ocular and bucco-dental infections, they did not reach clinical use yet [54].…”

Tissue-dependent induction of antimicrobial peptide genes after body wall injury in house fly (<i>Musca domestica</i>) larvae

“…Furthermore, the same synthetic peptide synthesized using ᴅ-amino acids displayed a higher antimicrobial activity than its ʟ-form counterpart (22,23). The potential utility of AMPs as an adjuvant has been examined because of their activity to induce immune responses in mammals (24)(25)(26). These observations demonstrate the importance of natural AMPs as medicinal resources.…”