Development of a Ligand-Directed Approach To Study the Pathogenesis of Invasive Aspergillosis

Invasive aspergillosis is a leading cause of infectious death in immunosuppressed patients. Here, we adapted a phage display library-based selection to screen and identify binding peptides to the surface of Aspergillus fumigatus conidia and hyphae. We identified a peptide (sequence CGGRLGPFC) that reliably binds to the surface of Aspergillus fumigatus hyphae. Binding was not Aspergillus strain specific, as it was also observed in hyphae of other Aspergillus clinical isolates. Furthermore, CGGRLGPFC-displaying phage targets Aspergillus fumigatus hyphae on formalin-fixed paraffin-embedded histopathology sections of lung tissue recovered from mice with invasive pulmonary aspergillosis. This approach may yield reagents such as peptidomimetics for novel diagnostic and therapeutic interventions in invasive aspergillosis. Invasive aspergillosis, mainly caused by Aspergillus fumiga-tus, is the most common opportunistic mycosis in immunosup-pressed patients with leukemia, bone marrow and solid-organ transplant recipients and a frequent cause of morbidity and mortality (17, 20). As the pathogenesis of invasive aspergillosis involves inhalation of airborne conidia in susceptible hosts, pneumonia is the most common clinical manifestation (17, 20)