Promising new approach for rapid diagnosis of Invasive Aspergillosis

Scientists in San Antonio, Texas, presenting at the recent 5oth ICAAC conference in Boston, have been investigating a new approach looking at secreted proteases from Aspergillus fumigatus, hoping to find a more rapid diagnosis of invasive aspergillosis (IA). The A. fumigatus genome secretes nearly 100 proteases many of which are secreted in vivo during infection.

By designing fluorogenically labelled substrates for these enzymes – the protease activity in either the serum or broncheolar lavage fluid can be tested in infected patients, using the unique thermotolerance of Aspergillus proteases to distinguish them from host proteases.

The technique requires the identification of fungus specific substrates which were identified using a library of fluorescent probe/substrates in comparison with human serum. The tests were carried out in a guinea pig model of invasive aspergillus where a number of substrate probes proved specific for the A. fumigatus proteases at temperatures up to 50C.
The next stage of the work will be to identify which labelled substrates may be specifically broken down by fungal proteases during infection – these would be promising diagnostic candidates.

Fluorogenic probes have already been used successfully to image protease activity in oncology and in inflammation, if successful this paves the way for alternative methods for rapid diagnosis of IA and potentially for following the progress of treatment as well.