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

在英国，耐甲氧西林金黄色葡萄球菌（MRSA）感染给个人、家庭和NHS带来了巨大的个人和经济成本（估计每年约10亿美元）。最近出现了新的社区获得性MRSA （CA-MRSA）菌株，在健康的年轻人中引起严重感染。CA-MRSA含有大量毒素，可以破坏人体宿主的防御能力，损害人体组织，其中包括一种叫做潘通-瓦伦丁白细胞杀死素（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，部分原因是主要制药公司不愿开发昂贵的新药，因为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的感染特异性生活方式。作为一个群体，金黄色葡萄球菌使用化学信号来决定何时产生毒素。我们正在试图了解感染期间影响毒素产生的因素。我们的最终目标是开发药物，通过干扰这种化学信号系统来阻止毒素的产生。这些药物也不太可能促进耐药性。

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.