The activity and action mechanism of novel short selective LL-37-derived anticancer peptides against clinical isolates of Escherichia coli.

Human cathelicidin LL-37 has recently attracted interest as a potential therapeutic agent, mostly because of its ability to kill a wide variety of pathogens and cancer cells. In this study, we aimed to investigate the antibacterial activity and cytotoxicity of previously designed LL-37 anticancer derivatives (i.e., P7, P22, and P38). Calcein release assay and field emission-scanning electron microscopy (FE-SEM) were performed to elucidate the possible mechanism of action of P38, the peptide with the highest bactericidal activity. In silico analysis demonstrated the amphipathic alpha-helical structure for three peptides. Antibacterial activity of P38 against multidrug-resistant (MDR) clinical isolates of Escherichia coli was higher than that of P7 and P22. P38 caused no hemolysis or cytotoxicity. Treating calcein-loaded E. coli with 4× MIC of P38 resulted in more than 96% leakage of calcein. Noticeably, FE-SEM revealed that P38 killed E. coli by disrupting the bacterial membrane. Molecular docking studies showed that P38 had a much higher affinity for the outer membrane of Gram-negative bacteria compared with both P22 and P7. Owing to the bactericidal activity of P38 against MDR E. coli isolates and its negligible cytotoxicity, P38 has the potential for further studies in a mouse model of infectious disease.