Mass Spectrometry-Based Analysis of Mice Infected with Aspergillus fumigatus

摘要

Aspergillus fumigatus is a fungus that is present predominately in decaying vegetation and soil. An average person breathes in a few hundred conidia (asexual, non-motile spores) a day, which are cleared by a healthy immune system effectively. Immunocompromised patients, however, may develop invasive aspergillosis (IA), a potentially fatal disease. Most commonly, IA causes primary pulmonary disease after A. fumigatus spores enter the lung through inhalation. IA often occurs in patients who have undergone hematopoietic stem cell or solid organ transplantation, received chemotherapy, or suffer from late-stage AIDS. Delay in initiation of antifungal therapy causes higher mortality. Current diagnostic criteria rely uponmicrobiologic, histologic, radiographic and carbohydrate biomarker assays. Some of these tests are time-consuming, others are invasive and each has variable accuracy. Consequently, patients with IA often receive treatment too late. In addition, A. fumigatus infection can lead to other diseases such as aspergilloma, in which A. fumigatus grows inside lung cavities, or allergic bronchopulmonary aspergilloma (ABPA), an allergic response to A. fumigatus. The organism may also colonize the airways without causing disease. Hence, development of a fast, sensitive, and less invasive diagnostic technique is critical in being able to correctly and confidently identify IA in patients soon after onset of symptoms. The goal of the present study is to identify A. fumigatus proteins that are specifically present in the organism of a patient during IA. Because there is no experimental model for colonization, A. fumigatus protein expression in biological samples from mice with IA is being compared to that from mice with fungal asthma. Identification of target proteins present in biological samples will help develop future diagnostic tools.