Maturation and resolution of Staphylococcus aureus skin abscess

据估计，全球每年有110万人死于金黄色葡萄球菌（S. aureus）感染。这使它成为每年造成第二大死亡人数的细菌病原体，仅次于结核病（160万人死亡）。鉴于有效疫苗开发的失败和耐药菌株（如MRSA）发病率的上升，金黄色葡萄球菌感染仍然是对人类健康的一个积极挑战。金黄色葡萄球菌感染的主要特征之一是脓肿的形成；细菌和充满脓液的病变带纤维囊。它们在广泛的组织中形成，从浅表组织（如皮肤）到内脏组织（如肌肉、脑、肺、肝）。金黄色葡萄球菌脓肿愈合非常缓慢，通常需要手术引流和/或延长静脉注射抗生素疗程。反过来，这可能导致抗生素耐药性和其他风险（例如，导管相关感染、药物毒性和艰难梭菌感染）。对于发展中经济体的卫生系统来说，充分治疗这些感染的卫生保健费用可能令人望而却步。此外，在发达国家，这些感染严重影响边缘化社区（例如静脉注射吸毒者），并经常在机构（例如监狱）中引起疫情。尽管脓肿是葡萄球菌感染的一种常见和严重的形式，但其生物学尚未得到充分的探索，特别是从免疫系统如何协调和解决这些感染的角度来看。该项目的目的是提供人体如何自然解决皮肤感染的关键步骤的详细特征。我们从中获得的见解将使我们能够为这些难以治疗的感染确定新的治疗目标，帮助它们更快地解决。这项工作的最终目的是改善患者的预后，减少我们对长期抗生素和手术的依赖。这项工作可能为引起脓肿的其他感染提供额外的见解，也可能为皮肤免疫解决机制提供见解，这可能对各种皮肤病的治疗有影响。

Staphylococcus aureus (S. aureus) infections have been estimated to cause 1.1 million deaths worldwide annually. This makes it the bacterial pathogen causing the second largest number of deaths annually, after tuberculosis (1.6 million deaths). Given failures in effective vaccine development and the rising incidence of resistant strains (e.g. MRSA), S. aureus infection remains an aggressive challenge to human health. One of the key features of S. aureus infection is the formation of abscesses; bacteria and pus-filled lesions with a fibrous capsule. These form in a broad range of tissues, from the superficial (e.g. skin) to the visceral (e.g. muscle, brain, lung, liver). S. aureus abscesses are very slow to resolve and often require surgical drainage and/or prolonged courses of intravenous antibiotics. In turn, this can lead to antibiotic resistance and additional risks (e.g. catheter-associated infection, drug toxicity and Clostridium difficile infection). The healthcare costs for adequately treating these infections can be prohibitive for health systems in developing economies. Additionally, in the developed world, these infections significantly impact marginalised communities (e.g. intravenous drug users) and frequently cause outbreaks in institutions (e.g. prisons).Despite being a common and serious form of Staphylococcal infection, the biology of abscess has been remarkably unexplored, particularly from the perspective of how the immune system co-ordinates and resolves these infections. The aim of this project is to deliver a detailed characterisation of the key steps involved in how the body naturally resolves these infections in the skin. Insights we gain from this will allow us identify new treatment targets for these difficult to treat infections, helping them resolve faster. This work ultimately aims to improve outcomes for patients and reduce our reliance on prolonged antibiotics and surgery. This work may offer additional insights for other infections causing abscess and also offer insights into mechanisms of immune resolution in the skin generally, which may have implications for the treatment of a variety of dermatological conditions.