Synergistic antibiotic effect of looped antimicrobial peptide CLP-19 with bactericidal and bacteriostatic agents

The treatment of drug-resistant infections is complicated and the alarming rise in infectious diseases poses a unique challenge for development of effective therapeutic strategies. Antibiotic-induced liberation of the bacterial endotoxin lipopolysaccharide (LPS) may have immediate adverse effects promoting septic shock in patients. In the present study, we first confirmed our previous finding that looped antimicrobial peptide CLP-19 exerts non-specific direct antibacterial activity with no toxic to mammalian cells and second revealed that CLP-19 has synergistic effect to enhance the antibacterial activities of other conventional bactericidal (ampicillin and ceftazidime) and bacteriostatic (erythromycin and levofloxacin) agents. Third, the underlying mechanism of antibiotic effect was likely associated with stimulation of hydroxyl radical generation. Lastly, CLP-19 was shown to effectively reduce the antibiotic-induced liberation of LPS, through direct neutralization of the LPS. Thus, CLP-19 is a potential therapeutic agent for combinatorial antibiotic therapy.