Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Amino Acids. 2018 Nov;50(11):1617-1628. doi: 10.1007/s00726-018-2638-z. Epub 2018 Aug 25.
We have already established that a short cationic peptide (CM11) has high antimicrobial activity against a number of bacterial pathogens. Considering the untreatable problem of burn infections caused by Pseudomonas aeruginosa and Acinetobacter baumannii, this study evaluated and compared antibacterial effects of the CM11 peptide and 1% silver-doped bioactive glass (AgBG) against extensively drug-resistant strains of these bacteria which were isolated from burn patients. Accordingly, the bacteria were isolated from burn patients and their antibiotic resistance patterns and mechanisms were fully determined. The isolated bacterial from patients were resistant to almost all commonly used antibiotics and silver treatment. The isolates acquired their resistance through inactivation of their porin, the overexpression of efflux pump, and beta-lactamase. CM11 peptide and 1% AgBG had minimum inhibitory concentration (MIC) of ≥ 16 μg ml and ≥ 4 mg ml for clinical isolates, respectively. The minimum bactericidal concentration (MBC) of peptide and 1% AgBG for resistant bacteria was ≥ 32 μg ml and ≥ 4 mg ml, respectively. Among the clinical isolates, two P. aeruginosa isolates and one A. baumannii isolate were resistant to 1% AgBG disk. The CM11 peptide also showed high biocompatibility in vivo and no cytotoxicity against fibroblasts and adipose-derived mesenchymal stem cells in concentrations ≤ 64 μg ml and ≤ 32 μg ml, respectively, while the safe concentration of 1% AgBG for these cells was ≤ 16 μg ml. In conclusion, these findings indicated that the 1% silver is not safe and effective for treatment of such infections. The data suggest that CM11 peptide therapy is a reliable and safe strategy that can be used for the treatment of burn infections caused by antimicrobial-resistant isolates. The next stage of the study will be a multicenter clinical trial.
我们已经证实,一种短的阳离子肽(CM11)对许多细菌病原体具有高抗菌活性。考虑到铜绿假单胞菌和鲍曼不动杆菌引起的烧伤感染无法治愈的问题,本研究评估并比较了 CM11 肽和 1%载银生物活性玻璃(AgBG)对从烧伤患者中分离出的这些细菌的广泛耐药菌株的抗菌效果。因此,从烧伤患者中分离出细菌,并充分确定其抗生素耐药模式和机制。从患者中分离出的细菌对几乎所有常用抗生素和银处理都有耐药性。这些耐药株通过孔蛋白失活、外排泵过度表达和β-内酰胺酶获得耐药性。CM11 肽和 1%AgBG 对临床分离株的最低抑菌浓度(MIC)分别为≥16μg/ml 和≥4mg/ml。肽和 1%AgBG 对耐药菌的最低杀菌浓度(MBC)分别为≥32μg/ml 和≥4mg/ml。在临床分离株中,2 株铜绿假单胞菌和 1 株鲍曼不动杆菌对 1%AgBG 药敏纸片有耐药性。CM11 肽在体内也表现出很高的生物相容性,在浓度≤64μg/ml 和≤32μg/ml 时对成纤维细胞和脂肪间充质干细胞无细胞毒性,而 1%AgBG 对这些细胞的安全浓度为≤16μg/ml。总之,这些发现表明 1%银对这些感染的治疗并不安全和有效。数据表明,CM11 肽治疗是一种可靠和安全的策略,可用于治疗由抗微生物药物耐药分离株引起的烧伤感染。下一阶段的研究将是一项多中心临床试验。