Department of Microbiology, University College Cork, Cork, Ireland.
BMC Microbiol. 2013 Sep 26;13:212. doi: 10.1186/1471-2180-13-212.
The emergence of bacterial drug resistance encourages the re-evaluation of the potential of existing antimicrobials. Lantibiotics are post-translationally modified, ribosomally synthesised antimicrobial peptides with a broad spectrum antimicrobial activity. Here, we focussed on expanding the potential of lacticin 3147, one of the most studied lantibiotics and one which possesses potent activity against a wide range of Gram positive species including many nosocomial pathogens. More specifically, our aim was to investigate if lacticin 3147 activity could be enhanced when combined with a range of different clinical antibiotics.
Initial screening revealed that polymyxin B and polymyxin E (colistin) exhibited synergistic activity with lacticin 3147. Checkerboard assays were performed against a number of strains, including both Gram positive and Gram negative species. The resultant fractional inhibitory concentration (FIC) index values established that, while partial synergy was detected against Gram positive targets, synergy was obvious against Gram negative species, including Cronobacter and E. coli.
Combining lacticin 3147 with low levels of a polymyxin could provide a means of broadening target specificity of the lantibiotic, while also reducing polymyxin use due to the lower concentrations required as a result of synergy.
细菌耐药性的出现促使人们重新评估现有抗菌药物的潜力。类细菌素是经过翻译后修饰的、核糖体合成的具有广谱抗菌活性的抗菌肽。在这里，我们专注于扩大乳链菌肽 3147 的潜力，乳链菌肽 3147 是研究最多的类细菌素之一，对包括许多医院病原体在内的多种革兰氏阳性物种具有强大的活性。更具体地说，我们的目的是研究当乳链菌肽 3147 与一系列不同的临床抗生素联合使用时，其活性是否可以增强。
初步筛选显示，多粘菌素 B 和多粘菌素 E（粘菌素）与乳链菌肽 3147 表现出协同活性。针对多种菌株进行棋盘试验，包括革兰氏阳性和革兰氏阴性物种。所得的部分抑菌浓度（FIC）指数值表明，虽然对革兰氏阳性靶标检测到部分协同作用，但对革兰氏阴性物种，包括克罗诺杆菌和大肠杆菌，协同作用明显。
将乳链菌肽 3147 与低水平的多粘菌素联合使用，可以提供一种扩大类细菌素靶特异性的方法，同时由于协同作用导致所需浓度降低，也减少了多粘菌素的使用。
