The LL-37 Antimicrobial Peptide as a Treatment for Systematic Infection of Acinetobacter baumannii in a Mouse Model.

Abstract

The antimicrobial peptides (AMPs) played a critical role in the innate immunity of the host and are considered natural sources illustrating a broad-spectrum antimicrobial activity with high specificity and low cytotoxicity. AMPs generally possess a net positive charge and have amphipathic structures. Thus, AMPs can bind and interact with negatively charged bacterial cell membranes, leading to destructive defects in biomembranes and ending in cell death. LL37 is the only human cathelicidin-derived antimicrobial peptide that shows a broad spectrum of antimicrobial activity. To determine the antibacterial efficiency of LL37 in a mouse model of systemic A. baumannii infection, LL37 corresponding gene was expressed in E. coli, purification and refolding situations were optimized. The antimicrobial performance of produced LL-37 against A. baumannii was evaluated in vitro via MIC and Time Kill assays, and its destructive effects on the bacterial cell were confirmed by SEM image. The recombinant LL37 showed strong antibacterial function against A. baumannii at 1.5 μg/mL concentration. Time kill assay showed a sharp reduction of cell viability during the first period of exposure, and complete cell death was recorded after 40 min exposure. Furthermore, in vivo results represented a significant ability of LL37 in the treatment of systematic infected mouse models, and all infected mice receiving LL37 protein survived without no trace of bacteria in their blood samples.