Department of Life Sciences, University of Trieste, Via Giorgieri 1, 34127 Trieste, Italy.
BMC Microbiol. 2010 Jun 23;10:178. doi: 10.1186/1471-2180-10-178.
Bac7 is a proline-rich peptide with a potent in vitro antimicrobial activity against Gram-negative bacteria. Here we investigated its activity in biological fluids and in vivo using a mouse model of S. typhimurium infection.
The efficacy of the active 1-35 fragment of Bac7 was assayed in serum and plasma, and its stability in biological fluids analyzed by Western blot and mass spectrometry. The ability of the peptide to protect mice against Salmonella was assayed in a typhoid fever model of infection by determination of survival rates and bacterial load in liver and spleen of infected animals. In addition, the peptide's biodistribution was evaluated by using time-domain optical imaging. Bac7(1-35) retained a substantial in vivo activity showing a very low toxicity. The peptide increased significantly the number of survivors and the mean survival times of treated mice reducing the bacterial load in their organs despite its rapid clearance.
Our results provide a first indication for a potential development of Bac7-based drugs in the treatment of salmonellosis and, eventually, other Gram-negative infections. The in vivo activity for this peptide might be substantially enhanced by decreasing its excretion rate or modifying the treatment schedule.
Bac7 是一种富含脯氨酸的肽，对革兰氏阴性菌具有强大的体外抗菌活性。在这里，我们使用鼠伤寒沙门氏菌感染模型研究了其在生物体液和体内的活性。
通过 Western blot 和质谱分析，检测了 Bac7 活性 1-35 片段在血清和血浆中的功效，并分析了其在生物体液中的稳定性。通过测定感染动物肝脏和脾脏中的存活率和细菌载量，检测了肽保护小鼠免受沙门氏菌感染的能力。此外，通过使用时域光学成像评估了肽的生物分布。 Bac7(1-35)保留了显著的体内活性，表现出极低的毒性。尽管肽迅速清除，但它增加了存活者的数量和接受治疗的小鼠的平均存活时间，降低了其器官中的细菌负荷。
我们的结果为基于 Bac7 的药物在治疗沙门氏菌病和最终其他革兰氏阴性感染方面的潜在开发提供了第一个迹象。通过降低其排泄率或修改治疗方案，可能会大大增强该肽的体内活性。
