LL37-rIb-AMP4 Hybrid Peptide as a Therapy for SystemicInfections of Acinetobacter baumannii, Pseudomonas aeruginosa,Vancomycin-Resistant Enterococcus (VRE), and Methicillin-ResistantStaphylococcus aureus (MRSA) Cells in a Mouse Model

Background: antimicrobial peptides (amps) are beneficial compounds that could be used asa new and effective method to suppress microbes. both ib-amp4 and ll37 are antimicrobialpeptides with a wide range of antimicrobial activities. this research aimed to evaluate theantibacterial potential of ll37-rib-amp4 hybrid protein as an antimicrobial agent againstpathogenic bacteria. therefore, its antibacterial effects against acinetobacter baumannii,pseudomonas aeruginosa, vancomycin-resistant enterococcus (vre), and methicillinresistantstaphylococcus aureus (mrsa) were investigated in vivo and in vitro.materials & methods: in this study, antimicrobial peptides rib-amp4, ll37, and ll37-rib-amp4 were expressed, purified, and refolded, and their synergistic and antibacterial effectsin combination with each other (ll37+rib-amp4) and as fusion proteins (ll37-rib-amp4)were tested against a. baumannii, p. aeruginosa, vre, and mrsa cells in vitro (mic, time kill,and sem) and against p. aeruginosa and vre cells in vivo.findings: ll37-rib-amp4 protein with molecular weight= 28 kd was correctly producedand purified. despite the lack of synergistic effects between ll37 and rib-amp4 peptidesin vitro, the stability test results showed higher stability for ll37-rib-amp4 hybrid protein.the findings of in vivo tests confirmed that all infected mice were improved with ll37-rib-amp4 and no signs of bacteria were observed in their blood and spleen samples. also, theseresults confirmed the stability and higher activity of ll37-rib-amp4 than the single form ofthese proteins.conclusion: considering the antimicrobial potential of the produced proteins, it seems thatthe recombinant ll37-rib-amp4 protein could be considered and used as a stable and activeantimicrobial drug in future studies.