Aspergillus is one of the most common fungal pathogens affecting neutropenic patients and other types of immunocompromised individuals such as those with Chronic Granulomatous Disease(CGD) of Childhood. Among a dozen species of Aspergillus reported to cause infection in humans, A. fumigatus is the most common species reported to cause invasive aspergillosis. All Aspergillus species propagate by conidia (spores), which humans encounter daily through inhalation. During 2007-2008, we investigated the Aspergillus response to host immune cells by studying the genes differentially expressed in conidia vs hyphae when challenged with neutrophils from healthy donors as well as from those with chronic granulomatous disease (CGD). To our knowledge, this is the first study that investigated the genes differentially expressed in conidia vs hyphae of A. fumigatus in response to neutrophils from healthy donors as well as from those with CGD which are defective in the production of reactive oxygen species. Upon exposure to either normal or CGD neutrophils, 244 genes were up-regulated in conidia but not in hyphae. Several of these genes are involved in the degradation of fatty acids, peroxisome function and the glyoxylate cycle which suggests that conidia exposed to neutrophils reprogram their metabolism to adjust to the host environment. In addition, the mRNA levels of four genes encoding proteins putatively involved in iron/copper assimilation were found to be higher in conidia and hyphae exposed to normal neutrophils compared to those exposed to CGD neutrophils. Deletants of several of these differentially expressed genes showed phenotypes related to the proposed functions, i.e. deletants of genes involved in fatty acid catabolism showed defective growth on fatty acids and the deletants of iron/copper assimilation showed a higher sensitivity to the oxidative agent menadione. None of these deletants, however, showed reduced resistance to neutrophil attack. During 2008-2009, we characterized the differences in disease manifestations and the manner of dissemination beween A. fumigatus and its sister species, A. udagawae. Both A. udagawae (Neosartorya udagawae) and A. fumigatus belong to Section Fumigatii in the genus Aspergillus and they can not be differentiatd by their morphological characteristics but can be differentiated by genetic methods. We also characterized the biological differences between the two species.
NIH ExPorter
NIH ExPorter