Does variable exotoxin expression alter outcome in Panton Valentine Leukocidin associated S. aureus infections?

可变的外毒素表达是否会改变潘顿·瓦伦丁杀白细胞素相关的金黄色葡萄球菌感染的结果？

• 批准号: G1000362/1
• 负责人: Tim Sloan
• 金额: $ 24.83万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Fellowship
• 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=G1000362%2F1
• 关键词: Does; variable; exotoxin; expression; alter

In the UK, Methicillin-Resistant Staphylococcus aureus (MRSA) infections are associated with enormous personal and financial costs to the individual, their family and to the NHS (estimated at around #1 billion p.a.). Recently new Community-Acquired MRSA (CA-MRSA) strains have emerged which cause severe infections in healthy young people. CA-MRSA have a larger armament of toxins which disable human host defences and damage human tissues, including a toxin called Panton-Valentine Leukocidin (PVL).Against this backdrop, the development of new classes of antibiotics has lagged far behind the urgent requirement for new drugs, in part because of the reluctance of major pharmaceutical companies to develop expensive new drugs that become rapidly obsolete through resistance. Consequently we need to gain better insights into the infection-specific lifestyle of bacteria if we are to discover new ways of preventing and treating infections.S. aureus bacteria use chemical signals to make decisions as a group about when to produce toxins. We are seeking to understand what factors influence toxin production during an infection. Ultimately our aim is to develop drugs that will disable the production of toxins by interfering with this chemical signalling system. Such drugs are also less likely to promote drug resistance.

在英国，耐甲氧西林金黄色葡萄球菌(MRSA)感染与个人、他们的家庭和NHS(估计每年约10亿美元)的巨大个人和经济成本有关。最近出现了新的社区获得性MRSA(CA-MRSA)菌株，这些菌株会导致健康年轻人的严重感染。CA-MRSA拥有更大的毒素武器，这些毒素会削弱人体宿主防御并损害人体组织，其中包括一种名为Panton-Valuine Leukosidin(PVL)的毒素。在这种背景下，新型抗生素的开发远远落后于对新药的迫切需求，部分原因是大型制药公司不愿开发昂贵的新药，这些新药由于耐药性而迅速过时。因此，如果我们要发现预防和治疗感染的新方法，我们需要更好地了解细菌感染特有的生活方式。金黄色葡萄球菌细菌使用化学信号作为一个群体来决定何时产生毒素。我们正在试图了解在感染过程中哪些因素会影响毒素的产生。最终，我们的目标是开发药物，通过干扰这种化学信号系统来阻止毒素的产生。这类药物也不太可能促进耐药性。