GSE143601 Reducing Aspergillus fumigatus virulence through targeted dysregulation of the conidiation pathway

Contributors : James I Stewart ; Vinicius M Fava ; Joshua D Keraert ; Adithya S Subramanian ; Fabrice N Gravelat ; Melanie Lehoux ; P L Howell ; Robert A Cramer ; Donald C SheppardSeries Type : Expression profiling by high throughput sequencingOrganism : Aspergillus fumigatusInhalation of conidia of the opportunistic mold  Aspergillus fumigatus by immunocompromised hosts can lead to invasive pulmonary disease. Inhaled conidia that escape immune defenses germinate to form filamentous hyphae that invade lung tissues. Conidiation rarely occurs during invasive infection of the human host, allowing the bulk of fungal en ergy to be directed towards vegetative growth. We hypothesized that forced induction of conidiation during infection can suppress A. fumigatus vegetative growth, impairing the ability of this organism to cause disease. To study the effects of conidiation pathway dysregulation on A. fumigatus vir ulence, a key transcriptional regulator of conidiation (brlA) was expressed under the control of a doxycycline-inducible promoter. Time- and dose-dependent brlA overexpression was observed in response to doxycycline both in vitro and in vivo. Exposure of the inducible brlA overexpression strain to low doses of doxycycline under vegetative growth conditions in vitro induced conidiation, while high doses arrested growth. Overexpression of brlA attenuated A. fumigatus virulence in both an invertebrate and mouse model of invasive aspergillosis. RNA sequencing stu...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Aspergillus fumigatus Source Type: research