Maturation and resolution of Staphylococcus aureus skin abscess

点击翻译按钮获取中文摘要

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.