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局部分离的广谱噬菌体在体内皮肤切除伤口模型中杀死耐甲氧西林金黄色葡萄球菌。

Locally isolated broad host-range bacteriophage kills methicillin-resistant Staphylococcus aureus in an in vivo skin excisional wound model in mice.

机构信息

Department of Biotechnology and Research Centre, Bapuji Institute of Engineering and Technology, Davangere, 577 004, Karnataka, India.

Oral Microbiology Research Laboratory, Faculty of Dentistry, Kuwait University, Kuwait.

出版信息

Microb Pathog. 2021 Mar;152:104744. doi: 10.1016/j.micpath.2021.104744. Epub 2021 Jan 20.

Abstract

From the perspective of an ever-increasing multidrug resistance among bacterial pathogens, bacteriophages are receiving renewed interest as potential alternative to antibiotics. We investigated the potential of a locally isolated species-specific phage against Staphylococcus aureus infection in a skin excisional wound model in mice. A significant time-dependent increase (P < 0.05) in wound healing was observed in the phage-treated mice groups. The animals treated with the phage ΦDMSA-2 exhibited a faster re-epithelialization and faster tissue re-modelling. Bacterial load in the infected tissue in all phage-treated groups diminished. The mean ± SD CFU per ml decreased from 3.3 × 10 ± 3.5 × 10 at day 1-1.43 × 10 ± 8.48 × 10 at day 16 (P < 0.05). The highest reduction in the bacterial load was observed in G5 (povidine-iodine treated) and G6 (povidine iodine + phage 10 PFU) groups as no bacterial counts were detected by day 12 in both groups. Interestingly, group G3, which was treated with a lower phage concentration (5 × 10 PFU), resulted in total clearing of the inoculated bacteria by day 16; while bacterial counts were still detected by that time in group G4, which was treated with a higher phage concentration of 10 PFU. Animals from phage-treated group G3 survived 100%, while those from the infected wound control group survived at a rate of 34% at day 9 and reached 0% by the end of day 22 (P < 0.001). The data from this study convincingly showed that phage treatment of the S. aureus-infected wounds resulted in a faster wound healing and a 100% survival of the animals. The results emphasize the utility of locally isolated species-specific phages in treatment against multidrug-resistant MRSA infections.

摘要

从细菌病原体日益增加的多药耐药性的角度来看,噬菌体作为抗生素的替代品重新引起了人们的兴趣。我们在小鼠皮肤切除伤口模型中研究了一种局部分离的特异性噬菌体对金黄色葡萄球菌感染的潜力。在噬菌体处理的小鼠组中,观察到伤口愈合有显著的时间依赖性增加(P<0.05)。用噬菌体 ΦDMSA-2 处理的动物表现出更快的再上皮化和更快的组织重塑。所有噬菌体处理组的感染组织中的细菌负荷都减少了。在第 1 天至第 16 天,每毫升的平均 ± 标准差 CFU 从 3.3×10±3.5×10 减少到 1.43×10±8.48×10(P<0.05)。在 G5(聚维酮碘处理)和 G6(聚维酮碘+噬菌体 10 PFU)组中观察到细菌负荷的最大减少,因为在这两组中,到第 12 天都没有检测到细菌计数。有趣的是,用较低噬菌体浓度(5×10 PFU)处理的 G3 组在第 16 天清除了接种的细菌;而在 G4 组(用 10 PFU 较高噬菌体浓度处理)中,到那时仍检测到细菌计数。用噬菌体处理的 G3 组的动物 100%存活,而感染伤口对照组的动物在第 9 天的存活率为 34%,在第 22 天结束时达到 0%(P<0.001)。本研究的数据令人信服地表明,噬菌体治疗金黄色葡萄球菌感染的伤口导致更快的伤口愈合和 100%的动物存活。结果强调了局部分离的特异性噬菌体在治疗多药耐药性 MRSA 感染方面的实用性。

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