The human antimicrobial peptide LL-37 and its fragments possess both antimicrobial and antibiofilm activities against multidrug-resistant Acinetobacter baumannii

• Published in: Peptides (New York, N.Y. : 1980) Vol. 49; pp. 131 - 137
• Main Authors: Feng, Xiaorong, Sambanthamoorthy, Karthik, Palys, Thomas, Paranavitana, Chrysanthi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2013
• Subjects: Acinetobacter baumannii; Acinetobacter baumannii - drug effects; Amino Acid Sequence; Anti-infective; antibacterial properties; Antiinfectives and antibacterials; antimicrobial peptides; Biofilm; Biofilms; Biofilms - drug effects; Cathelicidin; Cathelicidins - chemistry; Cathelicidins - pharmacology; cytotoxicity; Dispersion; Drug Resistance, Microbial; Drug Resistance, Multiple; drug therapy; Effectiveness; Fragments; Human; humans; Microbial Sensitivity Tests; minimum inhibitory concentration; Molecular Sequence Data; multiple drug resistance; Peptides; Strain; Cathelicidin; Biofilm; Acinetobacter baumannii; Anti-infective
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2013.09.007

•Antimicrobial peptide LL-37 and its fragments showed antibacterial activity against several drug-resistant Acinetobacter baumannii strains.•This peptide and two of its fragments also prevented biofilm formation by A. baumannii.•They may be considered as potential therapeutics for A. baumannii infections. Acinetobacter baumannii infections are difficult to treat due to multidrug resistance. Biofilm formation by A. baumannii is an additional factor in its ability to resist antimicrobial therapy. The antibacterial and antibiofilm activities of the human antimicrobial peptide LL-37 and its fragments KS-30, KR-20 and KR-12 against clinical isolates of multidrug-resistant (MDR) A. baumannii were evaluated. The minimal inhibitory concentration (MIC) of LL-37 against MDR A. baumannii isolates ranged from 16 to 32μg/mL. The MIC of KS-30 fragment varied from 8.0 to16μg/mL and the KR-20 fragment MIC ranged from 16 to 64μg/mL. LL-37 and KS-30 fragment exhibited 100% bactericidal activity against five A. baumannii strains, including four MDR clinical isolates, within 30min at concentrations of 0.25–1μg/mL. By 0.5h, the fragments KR-20 and KR-12 eliminated all tested strains at 8 and 64μg/mL respectively. LL-37 and its fragments displayed anti-adherence activities between 32-128μg/mL. A minimum biofilm eradication concentration (MBEC) biofilm assay demonstrated that LL-37 inhibited and dispersed A. baumannii biofilms at 32μg/mL respectively. Truncated fragments of LL-37 inhibited biofilms at concentrations of 64–128μg/mL. KS-30, the truncated variant of LL-37, effectively dispersed biofilms at 64μg/mL. At 24h, no detectable toxicity was observed at the efficacious doses when cytotoxicity assays were performed. Thus, LL-37, KS-30 and KR-20 exhibit significant antimicrobial activity against MDR A. baumannii. The prevention of biofilm formation in vitro by LL-37, KS-30 and KR-20 adds significance to their efficacy. These peptides can be potential therapeutics against MDR A. baumannii infections.