In vitro and in vivo studies on iminosugars as inhibitors of the biofilm formation by various bacteria pathogenic for humans (Enterococcus faecalis)

>>> Objective of the project: Biofilms are layers of bacteria that may infect medical equipment and prostheses that are placed in the human body and may also cause long-lasting, very difficult to treat infections in many locations in the body of the patients. The main problem with such infections is the fact that they are very difficult or impossible to treat, many times requiring removal of the implants or prostheses. Unlike drug resistant planktonic bacteria, there are no highly successful therapeutic strategies and the objective of this project is to propose substances which may in fact change this situation. The project is meant to test iminosugar anti-biofilm activity, as substances that could in the future be used to treat biofilm infections. >>> Description of the research to be carried out: Experiments will evaluate the activity of the tested iminosugar substances against typical biofilm forming bacteria which may often be isolated from patient infections. Different bacterial biofilms will be prepared in vitro and tested vs. iminosugars at different time intervals and observed using electron microscopy. Afterwards transcriptomic examination is planned, that will allow to show the bacterial cells reaction to iminosugars on a molecular level. Also planned are animal studies on murine and rat models of specific conditions, incl. wound infection and urinary tract infection. >>> Reasons for choosing the research topic: Currently, only antibiotics are available as substances to treat bacterial infections. Besides antibiotics, there are no highly successful biofilm treatment agents on the market. Nanotechnology which was viewed as a promising tool in treating infections and cancer (e.g. microrobots) before the turn of the millennium has not delivered that promise thus far. Therefore any project with a solid promise to improve that situation, considering the growing number of biofilm infections worldwide, should be viewed not as optional, but as necessary advancement of science and our medical knowledge. If successful, the study will lay foundations for future biofilm therapeutic agents.

本项目目标：生物被膜（Biofilms）是由细菌聚集形成的薄膜状结构，可污染植入人体的医疗设备与假体，还可在患者体内多个部位引发迁延不愈、极难治愈的感染。此类感染的核心难题在于其难以甚至无法治愈，多数情况下需取出植入物或假体。与耐药浮游细菌（planktonic bacteria）不同，目前尚无成熟有效的治疗策略，本项目旨在提出可切实改变这一现状的潜在物质。本项目将测试亚氨基糖（iminosugar）的抗生物被膜活性，以期未来将其用于治疗生物被膜相关感染。

拟开展研究内容：本实验将评估受试亚氨基糖类物质对临床患者感染中常见的典型生物被膜形成菌的活性。研究将通过体外培养构建不同的细菌生物被膜模型，于不同时间点用亚氨基糖进行干预，并借助电子显微镜进行观察。后续将开展转录组学检测，以从分子层面解析细菌细胞对亚氨基糖的应答反应。此外，本研究还计划构建特定感染模型的小鼠与大鼠动物实验，包括伤口感染与尿路感染模型。

选题依据：当前临床治疗细菌感染仅可使用抗生素类药物，除抗生素外，市场上尚无成熟有效的生物被膜感染治疗制剂。千禧年前后曾被视为治疗感染与癌症（如微型机器人）的极具前景的纳米技术，迄今尚未兑现其应用潜力。鉴于全球范围内生物被膜感染病例数持续增长，任何有望切实改善这一现状的研究项目，都不应被视为可选课题，而应视作推动科学与医学知识进步的必要举措。若本研究取得成功，将为后续生物被膜感染治疗制剂的研发奠定基础。