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- Title
Filamentous fungal carbon catabolite repression supports metabolic plasticity and stress responses essential for disease progression.
- Authors
Beattie, Sarah R.; Mark, Kenneth M. K.; Thammahong, Arsa; Ries, Laure Nicolas Annick; Dhingra, Sourabh; Caffrey-Carr, Alayna K.; Cheng, Chao; Black, Candice C.; Bowyer, Paul; Bromley, Michael J.; Obar, Joshua J.; Goldman, Gustavo H.; Cramer, Robert A.
- Abstract
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).
- Subjects
ASPERGILLUS fumigatus; MYCOSES; FUNGAL metabolism; DISEASE progression; LUNG infections; PHYSIOLOGICAL stress; FUNGI
- Publication
PLoS Pathogens, 2017, Vol 13, Issue 4, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1006340