Researchers tested the natural antimicrobial peptide LL-37 and two shorter versions called KE-18 and KR-12 against common infection‑causing microbes. The short peptides were better at killing the microbes in lab tests, and KE-18 could also stop biofilm formation even at low doses, without harming human red blood cells. This suggests KE-18 might become a useful anti‑infection ingredient, but it’s still far from a consumer product.

Amongst the recognized classes of naturally occurring antimicrobials, human host defense peptides are an important group with an advantage (given their source) that they should be readily translatable to medicinal products. It is also plausible that truncated versions will display some of the biological activities of the parent peptide, with the benefit that they are less costly to synthesize using solid-phase chemistry. The host defense peptide, LL-37, and two truncated mimetics, KE-18 and KR-12, were tested for their inhibitory effects and antibiofilm properties against <i>Candida albicans</i>, <i>Staphylococcus aureus</i>, and <i>Escherichia coli</i>, microorganisms commonly implicated in biofilm-related infections such as ventilator-associated pneumonia (VAP). Using <i>in silico</i> prediction tools, the truncated peptides KE-18 and KR-12 were selected for minimum inhibitory concentration (MIC) and antibiofilm testing on the basis of their favorable cationicity, hydrophobic ratio, and amphipathicity compared with the parent peptide. Two methods were analyzed for determining peptide efficacy against biofilms; a crystal violet assay and an XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] assay. The biocidal activities (measured by MIC) and antibiofilm activities (measured by a crystal violet assay) appeared to be independent. LL-37 had no biocidal action against <i>C. albicans</i> (MIC &gt; 250 &#x3bc;g/ml) but significant effects in both biofilm-prevention and biofilm-inhibition assays. KE-18 and KR-12 yielded superior MIC values against all three microorganisms. Only KE-18 had a significant effect in the biofilm-prevention assay, which persisted even at sub-MICs. Neither of the truncated peptides were active in the biofilm-inhibition assay. KE-18 was shown to bind lipopolysaccharide as effectively as LL-37 and to bind lipoteichoic acid more effectively. None of the peptides showed hemolytic activity against human erythrocytes at the concentrations tested. KE-18 should be considered for further development as a natural peptide-derived therapeutic for prevention of multi-species biofilm-related infections such as VAP.