title: Novel engineered cationic antimicrobial peptides display broad-spectrum activity against Francisella tularensis, Yersinia pestis and Burkholderia pseudomallei.
abstract: Broad-spectrum antimicrobials are needed to effectively treat patients infected in the event of a pandemic or intentional release of a pathogen prior to confirmation of the pathogen's identity. Engineered cationic antimicrobial peptides (eCAPs) display activity against a number of bacterial pathogens including multi-drug-resistant strains. Two lead eCAPs, WLBU2 and WR12, were compared with human cathelicidin (LL-37) against three highly pathogenic bacteria: Francisella tularensis, Yersinia pestis and Burkholderia pseudomallei. Both WLBU2 and WR12 demonstrated bactericidal activity greater than that of LL-37, particularly against F. tularensis and Y. pestis. Only WLBU2 had bactericidal activity against B. pseudomallei. WLBU2, WR12 and LL-37 were all able to inhibit the growth of the three bacteria in vitro. Because these bacteria can be facultative intracellular pathogens, preferentially infecting macrophages and dendritic cells, we evaluated the activity of WLBU2 against F. tularensis in an ex vivo infection model with J774 cells, a mouse macrophage cell line. In that model WLBU2 was able to achieve greater than 50% killing of F. tularensis at a concentration of 12.5 μM. These data show the therapeutic potential of eCAPs, particularly WLBU2, as a broad-spectrum antimicrobial for treating highly pathogenic bacterial infections.
authors.affiliation: Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Suha
authors.initials: S
authors.lastname: Abdelbaqi
authors.affiliation: Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Berthony
authors.initials: B
authors.lastname: Deslouches
authors.affiliation: Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Steckbeck
authors.affiliation: Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Montelaro
authors.affiliation: Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Reed
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology*; D016957:Burkholderia pseudomallei / Q000187:drug effects* / Q000502:physiology; D005604:Francisella tularensis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008826:Microbial Sensitivity Tests; D015010:Yersinia pestis / Q000187:drug effects* / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides