Li Di, Yang Ya, Tian Zhiqiang, Lv Jun, Sun Fengjun, Wang Qian, Liu Yao, Xia Peiyuan
Department of Pharmacy, Southwest Hospital, Third Military Medical University, Chongqing, China.
Department of Pharmacy, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Oncotarget. 2017 May 23;8(34):55958-55966. doi: 10.18632/oncotarget.18124. eCollection 2017 Aug 22.
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.
耐药性感染的治疗很复杂,传染病惊人的增长对有效治疗策略的开发构成了独特的挑战。抗生素诱导的细菌内毒素脂多糖(LPS)的释放可能会产生直接的不良影响,促使患者发生感染性休克。在本研究中,我们首先证实了我们之前的发现,即环状抗菌肽CLP-19具有非特异性直接抗菌活性,对哺乳动物细胞无毒,其次发现CLP-19具有协同作用,可增强其他传统杀菌(氨苄西林和头孢他啶)和抑菌(红霉素和左氧氟沙星)药物的抗菌活性。第三,抗生素作用的潜在机制可能与刺激羟基自由基的产生有关。最后,CLP-19被证明可通过直接中和LPS有效减少抗生素诱导的LPS释放。因此,CLP-19是联合抗生素治疗的潜在治疗剂。