Geisel School of Medicine
Aspergillus fumigatus is responsible for a disproportionate number of invasive mycosis cases relative to other common filamentous fungi. While many fungal factors critical for infection establishment are known, genes essential for disease persistence and progression are ill defined. We propose that fungal factors that promote navigation of the rapidly changing nutrient and structural landscape characteristic of disease progression represent untapped clinically relevant therapeutic targets. To this end, we find that A. fumigatus requires a carbon catabolite repression (CCR) mediated genetic network to support in vivo fungal fitness and disease progression. While CCR as mediated by the transcriptional repressor CreA is not required for pulmonary infection establishment, loss of CCR inhibits fungal metabolic plasticity and the ability to thrive in the dynamic infection microenvironment. Our results suggest a model whereby CCR in an environmental filamentous fungus is dispensable for initiation of pulmonary infection but essential for infection maintenance and disease progression. Conceptually, we argue these data provide a foundation for additional studies on fungal factors required to support fungal fitness and disease progression and term such genes and factors, DPFs (disease progression factors).
Beattie SR, Mark KMK, Thammahong A, Ries LNA, Dhingra S, Caffrey-Carr AK, Cheng C, Black CC, Bowyer P, Bromley MJ, Obar JJ, Goldman GH, Cramer RA. Filamentous fungal carbon catabolite repression supports metabolic plasticity and stress responses essential for disease progression. PLoS Pathog. 2017 Apr 19;13(4):e1006340. doi: 10.1371/journal.ppat.1006340. PMID: 28423062; PMCID: PMC5411099.
Dartmouth Digital Commons Citation
Beattie, Sarah R.; Mark, Kenneth; Thammahong, Arsa; Ries, Laure Nicolas Annick; Dhingra, Sourabh; Caffrey-Carr, Alayna; and Cheng, Chao, "Filamentous Fungal Carbon Catabolite Repression Supports Metabolic Plasticity and Stress Responses Essential for Disease Progression" (2017). Dartmouth Scholarship. 1718.