Modulation of beta-lactam resistance in methicillin-resistant Staphylococcus aureus by catechin gallates

儿茶素没食子酸酯对耐甲氧西林金黄色葡萄球菌的β-内酰胺耐药性的调节

• 批准号: G0600004/1
• 负责人: Peter Taylor
• 金额: $ 38.34万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0600004%2F1
• 关键词: Modulation; beta; lactam; resistance; methicillin

The introduction of antibacterial drugs into medical practice, which began in the 1930s and continued in spectacular fashion with the mass production of penicillin in the early 1940s gave rise to the belief that infectious diseases could be controlled and, eventually, mastered. However, the initial widespread optimism that antibiotics would banish serious infectious disease to the ?dustbin of history? has proven to be premature; infections remain the second leading cause of mortality worldwide and the major killer in the developing world. The reasons for the failure to defeat the threat from infection are many and complex but the emergence of antibiotic resistance has had an enormous impact on our ability to combat infection. Whenever a new antibiotic has been introduced, resistance has always followed. Bacteria have quickly found the means to counteract this threat to their survival and have developed ways to pass on their resistance genes to other bacteria. This acquired antibiotic resistance is responsible for the emergence of multi-resistant strains ? called ?superbugs? by the media ? that are now commonplace in hospitals and increasingly found in community acquired infections. Typical of these is MRSA, which has become a persistent and common permanent inhabitant of hospitals in the United Kingdom and elsewhere. While it is still sensitive to a few expensive antibiotics, there are well-founded fears that this may not last, in which case MRSA infections will become untreatable. We have been researching ways to reverse antibiotic resistance in MRSA, making it again sensitive to inexpensive antibiotics such as methicillin and oxacillin. These antibiotics prevent bacteria from making the rigid wall that they need to survive ? MRSA subverts this action by altering the way it makes its wall. We have found that a component of tea called ?ECg? interferes with the MRSA subverting machinery and converts the bacteria to methicillin sensitivity. Thus, ECg might be used in combination with oxacillin to restore antibiotic sensitivity. Unfortunately, ECg is rapidly broken down in the body but we have changed its chemical nature to make it resistant to breakdown and we have modified the compound in other ways to increase its attraction as a therapeutic. We now wish to understand better how ECg works against MRSA ? we know it inserts into the bacterial membrane - as deeper understanding of the processes involved will enable us to refine our most promising compounds and bring them closer to clinical use.

抗菌药物进入医疗实践始于20世纪30年代，并在20世纪40年代早期随着青霉素的大规模生产而以惊人的方式继续，这使人们相信传染病可以控制并最终被掌握。然而，最初人们普遍乐观地认为，抗生素将消除严重的传染病？历史的垃圾桶？感染仍是全世界第二大死亡原因，也是发展中国家的主要杀手。未能战胜感染威胁的原因很多，也很复杂，但抗生素耐药性的出现对我们抗击感染的能力产生了巨大影响。每当一种新的抗生素被引入，耐药性总是随之而来。细菌很快就找到了应对这种生存威胁的方法，并开发出了将其抗性基因传递给其他细菌的方法。这种获得性抗生素耐药性是多重耐药菌株出现的原因吗？叫什么超级细菌被媒体？现在在医院很常见，在社区获得性感染中也越来越多。其中典型的是MRSA，它已成为英国和其他地方医院的持久和常见的永久居民。虽然它仍然对一些昂贵的抗生素敏感，但有充分的理由担心这种情况可能不会持续，在这种情况下，MRSA感染将变得无法治疗。我们一直在研究逆转MRSA抗生素耐药性的方法，使其再次对甲氧西林和苯唑西林等廉价抗生素敏感。这些抗生素阻止细菌制造它们生存所需的刚性壁。MRSA通过改变其形成壁的方式来破坏这种行为。我们发现茶中有一种成分叫？心电图？干扰MRSA破坏机制并将细菌转化为甲氧西林敏感性。因此，ECG可与苯唑西林联合使用以恢复抗生素敏感性。不幸的是，心电图在体内迅速分解，但我们已经改变了它的化学性质，使其耐分解，我们已经修改了其他方式的化合物，以增加其作为治疗的吸引力。我们现在希望更好地了解ECG如何对抗MRSA？我们知道它会插入细菌的细胞膜，因为对所涉及的过程有更深入的了解，将使我们能够改进最有前途的化合物，使它们更接近临床应用。