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Characterization of a proteolytically stable multifunctional host defense peptidomimetic

Research output: Contribution to journalJournal articleResearchpeer-review

Rasmus D Jahnsen, Evan F Haney, Henrik Franzyk, Robert E W Hancock

The in vitro activity of a host defense peptidomimetic (HDM-4) was investigated. The compound exhibited an antimicrobial activity profile against a range of Gram-negative bacteria. HDM-4 permeabilized the outer membrane and partly depolarized the inner membrane at its minimal inhibitory concentration (MIC). Moreover, it was demonstrated that HDM-4 was distributed widely in the bacterial cell at lethal concentrations, and that it could bind to DNA. It was confirmed that the multimodal action of HDM-4 resulted in it being less likely to lead to resistance development as compared to single-target antibiotics. HDM-4 exhibited multispecies anti-biofilm activity at sub-MIC levels. Furthermore, HDM-4 modulated the immune response by inducing the release of the chemoattractants interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), and MCP-3 from human peripheral blood mononuclear cells. In addition, the compound suppressed lipopolysaccharide-mediated inflammation by reducing the release of the pro-inflammatory cytokines IL-6 and tumor necrosis factor-α.
Original languageEnglish
JournalChemistry & biology
Volume20
Issue number10
Pages (from-to)1286-1295
Number of pages10
ISSN1074-5521
DOIs
StatePublished - 10 Oct 2013

ID: 56064391