Developing novel approaches to treat trauma - associated fungal infections

[摘要] Traumatic injuries often result in infections leading to high morbidity and mortality. Fungal spores, the point of interest of this research, of species such as Mucormycetes, Scedosporium, Lomentospora, Fusarium and Candida, are ubiquitous in the environment. Here, we have taken a dual approach to investigate: 1) how two, novel treatments - acetic acid and blue light - are effective against those fungal species, and 2) how highly pathogenic and antifungal resistant species of Scedosporium and Lomentospora interact with innate immune cells. Firstly, I have demonstrated that low concentrations of acetic acid can inhibit spore germination as well as prevent growth of all fungal species tested. Therefore, acetic acid can be used as a potential preventative measure and/or treatment on infected wounds. Secondly, I have shown that blue light irradiation is effective against some, but not all fungal species, and should therefore be used with caution in a healthcare setting. In the latter part of this thesis I characterize the Scedosporium and Lomentospora interaction with macrophages. Using this system, I show for the first time that vomocytosis and lateral transfer are two distinct events and that these neglected fungal pathogens may hold interesting promise as a tool for understanding the fungal/host interaction. Lastly, I report on our preliminary attempts to establish a novel ex-vivo skin model and show that Langerhans cells within the epidermis do not mature nor release TNFα cytokine following infection with R. microsporus and S. apiospermum.

[发布机构] University:University of Birmingham;Department:Institute of Microbiology and Infection

[关键词] Q Science;QH Natural history;QH301 Biology