Abstract
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.
Highlights
The rapid emergence of drug-resistant bacteria endangers the efficacy of antibiotics, which presents a unique and alarming challenge to clinical care [1]
It is worth noting that CLP-19 showed antibacterial activity at minimum inhibitory concentrations (MICs) ranging from 16 ug/mL to 32 μg/mL against E. coli, S. aureus and A. baumannii, suggesting non-selective antibacterial activity for Gram-negative and Gram-positive bacteria
The present study confirmed our previous finding that CLP-19 exhibits a robust antibacterial activity against Gram-positive and Gram-negative bacteria
Summary
The rapid emergence of drug-resistant bacteria endangers the efficacy of antibiotics, which presents a unique and alarming challenge to clinical care [1]. The pathophysiology of septic shock is not entirely understood, it is likely due to liberation of endotoxins from the bacterial cell wall during destruction of the microorganism [2]. To overcome this obstacle, various adjuvant treatment approaches have been carefully analyzed, ranging from standard intravenous immunoglobulins or endotoxin corespecific antibodies to treatment with cytokines, cytokine receptor antagonists, or immunomodulators; the results, have been largely disappointing. Development of a novel adjuvant treatment that exhibits synergistic effect in combination with existing antibacterial agents but that relieves the excessive endotoxin-induced septic shock is a critical step in the battle against this serious threat to public health
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