Invasive aspergillosis (IA) is the most frequent infectious cause of death in leukemia and bone marrow transplant patients. The conidia of Aspergillus fumigatus, the filamentous fungus that is the most common cause of IA, are inhaled and germinate in the lung. Like all filamentous fungi A. fumigatus undergoes highly polar growth via germ tubes and later branches. This highly polar tip growth allows A. fumigatus to invade blood vessels and tissues resulting in the necrosis characteristic of IA. Despite the importance of polar growth to IA, little is known about the molecular mechanisms of polar growth in A. fumigatus. The proposed research will use microarray profiling to identify genes that are differentially transcribed and/or asymmetrically localized during polar growth in A. fumigatus. Temporal profiles of genes expressed during polar growth will be generated using RNA isolated from synchronous cultures just before and after germ tube and branch emergence and during elongation of hyphae and branches. Spatial profiles of genes expressed during polar growth will be generated using RNA isolated from specific regions of germ tubes, hyphae and branches with laser microcapture techniques. RNA will be labeled and hybridized to existing PFGRC A. fumigatus microarrays and expression patterns will be analyzed. Identification of genes that are differentially transcribed and/or asymmetrically localized during polar growth will lay the foundation for a comprehensive research program focusing on polar growth in A. fumigatus and its role in IA.
Invasive aspergillosis (IA), an often fatal disease of the immunocompromised, is caused when the spores of Aspergillus fumigatus are inhaled and grow in the lung. Like other filamentous fungi, A. fumigatus sends out long tubular cells known as hyphae into the environment searching for nutrients and in IA it is these hyphae which cause the destruction of host tissue. The proposed research will identify genes that allow A. fumigatus to make hyphae and so will uncover new ways of combating IA.
| Oda, Ken; Bignell, Elaine; Kang, S Earl et al. (2017) Transcript levels of the Aspergillus fumigatus Cdc42 module, polarisome, and septin genes show little change from dormancy to polarity establishment. Med Mycol 55:445-452 |
| Leal Jr, Sixto M; Vareechon, Chairut; Cowden, Susan et al. (2012) Fungal antioxidant pathways promote survival against neutrophils during infection. J Clin Invest 122:2482-98 |
| Leal Jr, Sixto M; Cowden, Susan; Hsia, Yen-Cheng et al. (2010) Distinct roles for Dectin-1 and TLR4 in the pathogenesis of Aspergillus fumigatus keratitis. PLoS Pathog 6:e1000976 |
