Overcoming Drug Resistance with Alginate Oligosaccharides Able To Potentiate the Action of Selected Antibiotics
Overcoming Drug Resistance with Alginate Oligosaccharides Able To Potentiate the Action of Selected Antibiotics
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DOI：
10.1128/aac.00525-12
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发表时间：
2012-10-01
影响因子：
4.9
通讯作者：
Thomas, David W.
中科院分区：
文献类型：
--
作者：
Khan, Saira;Tondervik, Anne;Thomas, David W.
不受控制且常常不恰当的抗生素使用导致抗生素耐药性病原体的流行不断增加，对美国和欧洲的医疗保健系统造成重大成本影响。我们描述了基于生物聚合物海藻酸盐的低分子量寡糖纳米药物 (OligoG) 的利用，它能够通过调节生物膜的形成和持久性并减少对抗生素治疗的耐药性来扰乱多重耐药 (MDR) 细菌，这一点通过传统和机器人 MIC 筛选和显微分析可以明显看出。 生物膜结构。 OligoG 提高了传统抗生素针对重要 MDR 病原体（包括假单胞菌、不动杆菌和伯克霍尔德杆菌）的功效（高达 512 倍），似乎对几类抗生素（即大环内酯类、β-内酰胺类和四环素类）有效。使用共焦激光扫描显微镜 (CLSM) 和扫描电子显微镜 (SEM)，显示增加藻酸盐低聚物浓度（2%、6% 和 10%）对所产生的生物膜的质量以及生物膜内细胞的健康有直接影响。 10% OligoG 存在时，生物膜生长明显减弱，生物量减少，细胞间隙增加，细菌细胞本身由于细胞膜明显受损而变得扭曲和不均匀。该报告证明了使用特定藻酸盐制剂降低伤口生物膜对抗生素耐受性的可行性。
The uncontrolled, often inappropriate use of antibiotics has resulted in the increasing prevalence of antibiotic-resistant pathogens, with major cost implications for both United States and European health care systems. We describe the utilization of a low-molecular-weight oligosaccharide nanomedicine (OligoG), based on the biopolymer alginate, which is able to perturb multidrug-resistant (MDR) bacteria by modulating biofilm formation and persistence and reducing resistance to antibiotic treatment, as evident using conventional and robotic MIC screening and microscopic analyses of biofilm structure. OligoG increased (up to 512-fold) the efficacy of conventional antibiotics against important MDR pathogens, including Pseudomonas, Acinetobacter, and Burkholderia spp., appearing to be effective with several classes of antibiotic (i.e., macrolides, beta-lactams, and tetracyclines). Using confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM), increasing concentrations (2%, 6%, and 10%) of alginate oligomer were shown to have a direct effect on the quality of the biofilms produced and on the health of the cells within that biofilm. Biofilm growth was visibly weakened in the presence of 10% OligoG, as seen by decreased biomass and increased intercellular spaces, with the bacterial cells themselves becoming distorted and uneven due to apparently damaged cell membranes. This report demonstrates the feasibility of reducing the tolerance of wound biofilms to antibiotics with the use of specific alginate preparations.