Disruption and Prevention of Bacterial Biofilms - Market Research Commercial Viability Study

细菌生物膜的破坏和预防 - 市场研究商业可行性研究

• 批准号: NE/I00761X/1
• 负责人: Grant Burgess
• 金额: $ 1.53万
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FI00761X%2F1
• 关键词: Disruption; Prevention; Bacterial; Biofilms; Market

The majority of the microscopic organisms (or microbes), such as bacteria and fungi, found in the environment grow in large communities enclosed in a layer of material called a biofilm. These microbial biofilms are frequently found in home, often as slimes growing on wet surfaces (such as bathroom tiles, taps and water pipes). Normally these biofilms pose little risk to people and can easily be removed by standard cleaning products. However, in both healthcare and industrial envirnoments, microbes growing in biofilms can cause a multitude of serious problems. In industrial environments the build up of slimes on surfaces leads to many different problems, such as the clogging of pipes and the fouling of machines. It is also the first step in the build up of barnacles and other sea creatures on the hulls of container ships. The growth of these creatures makes the hull rough and increases the ship's 'drag' through the water. This means the ship must use more fuel to go at the same speed, adding to CO2 emissions, to the cost of moving the cargo and ultimately the price of the transported goods. Much more serious problems can occur in healthcare environments. The slime layer of a biofilm encapsulates the microbe which made it. This provides a protective barrier between the microbe and its environment. In the case of a bacterial infection in a person (such as an MRSA wound infection, commonly found in recovering hospital patients) the biofilms are very difficult to remove and they make the infectious bacteria highly resistant to antibiotics. It is therefore extremely difficult to cure a bacterial biofilm infection often resulting in patient fatalities. In fact bacterial and fungal biofilms play a highly significant role in large number of medical conditions, from serious infectious diseases to chronic conditions such as Cystic Fibrosis. Biofilms are also involved in infections related to medical implants and even in every day health issues such as tooth decay and plaque build up. We are developing a new approach to fight biofilms. The microbes which make biofilms can also to disperse them, to allow the microbes to move to new places. Some microbes deliberately break up the biofilms formed by other competing microbes, in order to steal food or other resources. We are using these same techniques to break up biofilms. We have isolated a species of bacteria (from the sea) which releases a chemical (an enzyme) which breaks down a key part of the biofilms. This results in a break down of the whole biofilm and causes the target bacteria to disperse from their biofilm protected state. This enzyme also prevents the formation of new biofilms, thus it can be used in a pre-emptive preventative manner. We aim to explore methods to make this key enzyme cheaply and to test it in the break up of many different biofilms associated with diseases and industrial problems. The ultimate aim of this project will be to show that our enzyme can be used to solve specific biofilm related problems. An example would be using our enzyme to break up the biofilms in a patient who has a bacterial infection, followed by an antibiotic to kill the now more vulnerable bacteria. This would result in a new way to cure patients with certain bacterial infections.

在环境中发现的大多数微生物(或微生物)，如细菌和真菌，都生长在封闭在一层称为生物膜的材料中的大型群落中。这些微生物生物膜经常在家里发现，通常是在潮湿的表面(如浴室瓷砖、水龙头和水管)上生长的粘液。通常情况下，这些生物膜对人体的风险很小，可以很容易地用标准的清洁产品去除。然而，在医疗和工业环境中，生物膜中生长的微生物会导致许多严重的问题。在工业环境中，表面上堆积的泥浆会导致许多不同的问题，如管道堵塞和机器结垢。这也是在集装箱船的船体上建立藤壶和其他海洋生物的第一步。这些生物的生长使船体变得粗糙，并增加了船在水中的阻力。这意味着这艘船必须使用更多的燃料才能以同样的速度行驶，这会增加二氧化碳排放，增加运输货物的成本，并最终降低运输货物的价格。更严重的问题可能发生在医疗保健环境中。生物膜的粘液层包裹着制造它的微生物。这在微生物和它的环境之间提供了一种保护性屏障。在人的细菌感染(如MRSA伤口感染，通常在康复的医院患者中发现)的情况下，生物膜很难去除，它们使感染细菌对抗生素产生高度抗药性。因此，要治愈常常导致病人死亡的细菌生物膜感染是极其困难的。事实上，细菌和真菌生物膜在从严重的传染病到囊性纤维化等慢性疾病的大量医疗条件下发挥着非常重要的作用。生物膜还涉及与医疗植入物相关的感染，甚至在日常健康问题中，如龋齿和牙菌斑的积累。我们正在开发一种新的方法来对抗生物膜。制造生物膜的微生物也可以分散它们，让微生物移动到新的地方。一些微生物故意破坏其他相互竞争的微生物形成的生物膜，以窃取食物或其他资源。我们正在使用同样的技术来分解生物膜。我们(从海洋中)分离出一种细菌，这种细菌会释放一种化学物质(一种酶)，这种化学物质会分解生物膜的一个关键部分。这会导致整个生物膜的分解，并导致目标细菌从其生物膜保护状态中分散。这种酶还可以防止新生物膜的形成，因此它可以以先发制人的预防性方式使用。我们的目标是探索以低成本制造这种关键酶的方法，并在与疾病和工业问题相关的许多不同生物膜的分解中测试它。这个项目的最终目的将是证明我们的酶可以用来解决特定的生物膜相关问题。一个例子是，用我们的酶分解细菌感染患者的生物膜，然后用抗生素杀死现在更脆弱的细菌。这将导致一种新的方法来治愈某些细菌感染的患者。

项目成果

Crystal structure of NucB, a biofilm-degrading endonuclease.

• DOI: 10.1093/nar/gkx1170
• 发表时间: 2018-01-09
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Baslé A;Hewitt L;Koh A;Lamb HK;Thompson P;Burgess JG;Hall MJ;Hawkins AR;Murray H;Lewis RJ
• 通讯作者: Lewis RJ