A Novel Peptide-Based Antimicrobial Wound Treatment is Effective Against Biofilms of Multi-Drug Resistant Wound Pathogens.

Wound infections are a common complication of combat-related injuries that significantly increase morbidity and mortality. Multi-drug resistant (MDR) organisms and their associated biofilms play a significant role in the pathogenicity and chronicity of wound infections. A critical barrier to progress in the treatment of traumatic wounds is the need for broad spectrum antimicrobials that are effective against biofilms and compatible with topical delivery. In this study, we present the in vitro efficacy of two de novo designed cationic, antimicrobial peptides and related topical formulations against single species and polymicrobial biofilms of MDR bacteria. Minimum biofilm eradication concentrations for peptides ranged from 0.7 µM for Staphylococcus aureus to 13.2 µM for Pseudomonas aeruginosa. Varying pH did not adversely impact peptide activity, however, in the presence of albumin, minimum biofilm eradication concentrations generally increased. When formulated into gels or dressings, both peptides eradicated mono- and polymicrobial biofilms of MDR pathogens. The biocompatibility index (BI) was found to be greater than one for both ASP-1 and ASP-2, with a slightly greater (more favorable) BI for ASP-2. The BIs for both peptides were greater than BIs previously reported for commonly used topical antimicrobial agents. The antimicrobial peptides and related formulations presented provide a promising platform for treatment of wound biofilms to improve outcomes for those injured in combat.

Synthesis of hepcidin derivatives in order to develop standards for immune adsorption method.

MeCN, acetonitrile; ECL, enhanced chemiluminescence; EDT, 1,2-ethanedithiole; HEPC12-A, rabbit anti-human hepcidin IgG, affinity purified; HEPC13-A, rabbit anti-mouse/human hepcidin IgG, affinity purified; HEPC61-P, human hepcidin-25 control/blocking synthetic peptide; HRP, horseradish peroxidase; IL-6, interleukin-6; KLH, keyhole limpet hemocyanin; LEAP, liver-expressed antimicrobial peptide; NEM, N-ethylmaleimide; NMP, N-methyl-pirrolidone; PBS, phosphate buffered saline; PVDF, polyvinylidene difluoride; SELDI-TOF-MS, surface-enhanced laser desorption ionization-time-of-flight mass spectrometry; TMB, tetramethylbenzidin; TNF-alpha, tumor necrosis factor-alpha.

Protective efficacy of CAP18106-138-immunoglobulin G in sepsis.

Naturally present antibacterial proteins play an important role in innate host defense. A synthetic peptide mimicking the C-terminal lipopolysaccharide (LPS)-binding domain of rabbit cathelicidin CAP18 was coupled to immunoglobulin (Ig) G to create CAP18(106-138)-IgG, a construct that, in concentrations equimolar to those of peptide alone, binds and neutralizes LPS and kills multiple gram-negative bacterial strains. The protective efficacy of CAP18(106-138)-IgG was evaluated in a model of cecal ligation and puncture in mice. A single intravenous administration of 20 mg/kg CAP18(106-138)-IgG protected against mortality, compared with sham-coupled IgG (P<.03). There was no protection offered by administration of equimolar peptide alone (P=.96). There was a trend toward protection in C3H/HeJ mice that are minimally sensitive to LPS (P=.06), suggesting that direct detoxification of LPS was not the only mechanism of protection. Chemical or genetic coupling of antimicrobial peptides to IgG may be a means of using these peptides to treat infections.