Feng Q, Huang Y, Chen M, Li G, Chen Y
Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, 2699 Qianjin St., Changchun, Jilin, 130012, China.
National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, China.
Eur J Clin Microbiol Infect Dis. 2015 Jan;34(1):197-204. doi: 10.1007/s10096-014-2219-3. Epub 2014 Aug 30.
In this study, the antimicrobial activities based on the synergistic effects of traditional antibiotics (imipenem, cefepime, levofloxacin hydrochloride and vancomycin) and antimicrobial peptides (AMPs; PL-5, PL-31, PL-32, PL-18, PL-29 and PL-26), alone or in combination, against three Gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumoniae and Staphylococcus epidermidis) and three Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae) were investigated. In addition, the antimicrobial activity that was based on the synergistic effects of levofloxacin hydrochloride and PL-5 against Staphylococcus aureus in vivo was explored in a mouse infection model. Traditional antibiotics and AMPs showed significant synergistic effects on the antibacterial activities against the different Gram-positive and Gram-negative bacteria in vitro. A strong synergistic effect in the PL-5 and levofloxacin hydrochloride combination against Staphylococcus aureus was observed in the mouse infection model in vivo. The mechanism of synergistic action was due to the different targets of AMPs and traditional antibiotics. The combination of AMPs and traditional antibiotics can dramatically enhance antimicrobial activity and may help prevent or delay the emergence of antibiotic resistance. Thus, this combination therapy could be a promising approach to treat bacterial infections, particularly mixed infections and multi-antibiotic-resistant infections, in the clinics.
在本研究中，研究了传统抗生素（亚胺培南、头孢吡肟、盐酸左氧氟沙星和万古霉素）与抗菌肽（AMPs；PL-5、PL-31、PL-32、PL-18、PL-29和PL-26）单独或联合使用对三种革兰氏阳性菌（金黄色葡萄球菌、肺炎链球菌和表皮葡萄球菌）和三种革兰氏阴性菌（铜绿假单胞菌、大肠杆菌和肺炎克雷伯菌）的抗菌活性。此外，在小鼠感染模型中探索了盐酸左氧氟沙星和PL-5联合使用对金黄色葡萄球菌的体内抗菌活性。传统抗生素和AMPs在体外对不同革兰氏阳性菌和革兰氏阴性菌的抗菌活性显示出显著的协同作用。在体内小鼠感染模型中，观察到PL-5和盐酸左氧氟沙星联合使用对金黄色葡萄球菌有很强的协同作用。协同作用的机制是由于AMPs和传统抗生素的靶点不同。AMPs与传统抗生素联合使用可显著增强抗菌活性，并可能有助于预防或延缓抗生素耐药性的出现。因此，这种联合治疗可能是临床上治疗细菌感染，特别是混合感染和多重耐药感染的一种有前景的方法。
