Park Seong-Cheol, Nam Joung-Pyo, Kim Jun-Ho, Kim Young-Min, Nah Jae-Woon, Jang Mi-Kyeong
Department of Polymer Science and Engineering, Sunchon National University, 255 Jungang-ro, Suncheon, Jeonnam 540-950, Korea.
Int J Mol Sci. 2015 Apr 10;16(4):7995-8007. doi: 10.3390/ijms16047995.
Recently, the number of patients infected by drug-resistant pathogenic microbes has increased remarkably worldwide, and a number of studies have reported new antibiotics from natural sources. Among them, chitosan, with a high molecular weight and α-conformation, exhibits potent antimicrobial activity, but useful applications as an antibiotic are limited by its cytotoxicity and insolubility at physiological pH. In the present study, the antibacterial activity of low molecular weight water-soluble (LMWS) α-chitosan (α1k, α5k, and α10k with molecular masses of 1, 5, and 10 kDa, respectively) and β-chitosan (β1k, β5k, and β10k) was compared using a range of pathogenic bacteria containing drug-resistant bacteria isolated from patients at different pH. Interestingly, β5k and β10k exhibited potent antibacterial activity, even at pH 7.4, whereas only α10k was effective at pH 7.4. The active target of β-chitosan is the bacterial membrane, where the leakage of calcein is induced in artificial PE/PG vesicles, bacterial mimetic membrane. Moreover, scanning electron microscopy showed that they caused significant morphological changes on the bacterial surfaces. An in vivo study utilizing a bacteria-infected mouse model found that LMWS β-chitosan could be used as a candidate in anti-infective or wound healing therapeutic applications.
近年来，全球范围内感染耐药致病微生物的患者数量显著增加，许多研究报道了从天然来源获得的新型抗生素。其中，具有高分子量和α-构象的壳聚糖表现出强大的抗菌活性，但其作为抗生素的实际应用受到细胞毒性和在生理pH下不溶性的限制。在本研究中，使用一系列包含从不同pH值患者中分离出的耐药菌的致病细菌，比较了低分子量水溶性（LMWS）α-壳聚糖（分别为分子量为1、5和10 kDa的α1k、α5k和α10k）和β-壳聚糖（β1k、β5k和β10k）的抗菌活性。有趣的是，β5k和β10k即使在pH 7.4时也表现出强大的抗菌活性，而只有α10k在pH 7.4时有效。β-壳聚糖的作用靶点是细菌膜，在人工PE/PG囊泡（细菌模拟膜）中可诱导钙黄绿素泄漏。此外，扫描电子显微镜显示它们会导致细菌表面出现显著的形态变化。利用细菌感染小鼠模型进行的体内研究发现，低分子量水溶性β-壳聚糖可用作抗感染或伤口愈合治疗应用的候选药物。
