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两种市售噬菌体制剂(葡萄球菌噬菌体和PYO噬菌体)对耐甲氧西林菌的抗菌效果:预防和根除生物膜形成以及控制幼虫的全身感染

Antibacterial Efficacy of Two Commercially Available Bacteriophage Formulations, Staphylococcal Bacteriophage and PYO Bacteriophage, Against Methicillin-Resistant : Prevention and Eradication of Biofilm Formation and Control of a Systemic Infection of Larvae.

作者信息

Tkhilaishvili Tamta, Wang Lei, Tavanti Arianna, Trampuz Andrej, Di Luca Mariagrazia

机构信息

Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Berlin Institute of Health, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.

Berlin-Brandenburg Center for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Berlin, Germany.

出版信息

Front Microbiol. 2020 Feb 7;11:110. doi: 10.3389/fmicb.2020.00110. eCollection 2020.

Abstract

Sessile bacteria growing on surfaces are more resistant to standard antibiotics than their planktonic counterpart. Due to their antimicrobial properties, bacteriophages have re-emerged as a promising approach to treat bacterial biofilm-associated infections. Here, we evaluated the ability of two commercially available phage formulations, Staphylococcal bacteriophage (containing the monophage Sb-1) and PYO bacteriophage (a polyphage), in preventing and eradicating an biofilm of methicillin-resistant (MRSA) by isothermal microcalorimetry and high-resolution confocal laser scanning microscopy (CLSM). Moreover, to assess the potential efficacy of both phage preparations, a model of MRSA systemic infection was used. Microcalorimetry measurement showed that 10 PFU/ml (the highest tested titer) of both phage formulations were able to inhibit planktonic growth in a concentration-dependent manner. However, MRSA biofilm was eradicated only by co-incubation of 5-7 days with the highest phage titers, respectively. In the experiments of biofilm prevention, isothermal microcalorimetry revealed that the heat production was completely abolished in the presence of sub-inhibitory titers (10 PFU/ml) of phages. These data were also confirmed by confocal laser scanning microscopy. Both phage formulations increased the survival of larvae preventing or treating MRSA infection compared to untreated control. In conclusion, tested phage formulations are promising for preventing device colonization and killing biofilm bacteria attached on a surface. Novel strategies for direct coating and release of phages from material should be investigated.

摘要

附着在表面生长的固着型细菌比浮游型细菌对标准抗生素更具抗性。由于其抗菌特性,噬菌体已重新成为治疗细菌生物膜相关感染的一种有前景的方法。在此,我们通过等温微量热法和高分辨率共聚焦激光扫描显微镜(CLSM)评估了两种市售噬菌体制剂,葡萄球菌噬菌体(含单噬菌体Sb - 1)和PYO噬菌体(一种多噬菌体)预防和根除耐甲氧西林金黄色葡萄球菌(MRSA)生物膜的能力。此外,为评估这两种噬菌体制剂的潜在疗效,使用了MRSA全身感染模型。微量热法测量表明,两种噬菌体制剂的10 PFU/ml(测试的最高滴度)都能够以浓度依赖的方式抑制浮游菌生长。然而,只有分别与最高噬菌体滴度共同孵育5 - 7天才能根除MRSA生物膜。在生物膜预防实验中,等温微量热法显示在噬菌体亚抑制滴度(10 PFU/ml)存在下热产生完全被消除。这些数据也得到了共聚焦激光扫描显微镜的证实。与未处理的对照相比,两种噬菌体制剂都提高了预防或治疗MRSA感染的幼虫的存活率。总之,测试的噬菌体制剂在预防装置定植和杀死附着在表面的生物膜细菌方面很有前景。应研究从材料直接包被和释放噬菌体的新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66a6/7018685/a7ea34585355/fmicb-11-00110-g001.jpg

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