Potential Diagnostic and Research Applications of a Recombinant Antibody Directed Against Ferrated Triacetylfusarinine C from Aspergillus fumigatus.

Although Aspergillus fumigatus has been identified as a critical fungal pathogen by the World Health Organization, diagnosis of the various types of aspergilloses remains unsatisfactory. New biomarkers of disease and accessible test systems are needed. Moreover, new treatment concepts are required to address infections caused by this invasive pathogen. Siderophore production by A. fumigatus offers opportunities for both improved diagnosis and potential therapy. Here, we report the development of a competitive ELISA that detects ferrated triacetylfusarinine C (FeTAFC) using a recombinant monoclonal IgG [anti-FeTAFC]. The FeTAFC ELISA can detect FeTAFC in human urine, a matrix proposed to be especially suitable for disease diagnosis because of the non-invasive nature of specimen collection. In addition, a novel assay was developed to assess the in vitro inhibitory properties of the IgG [anti-FeTAFC] towards A. fumigatus mutant and wild-type growth under iron-limiting conditions. The growth of A. fumigatus ΔsidD, deficient in TAFC and precursor fusarinine C (FsC) biosynthesis, was significantly reduced (p = 0.0003) in the presence of the antibody. While the growth of A. fumigatus wild-type was less affected in the presence of the antibody, the ratio of secreted TAFC:FsC was increased due to increased conversion of FsC to TAFC-likely because of extracellular complexation of FeTAFC by the IgG [anti-FeTAFC]. This work shows the utility of the IgG [anti-FeTAFC] for the detection of A. fumigatus and initial evidence for limiting fungal growth by attenuation of FeTAFC uptake.