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FEMS Microbiol Lett. 2013 Aug;345(2):77-84. doi: 10.1111/1574-6968.12181. Epub 2013 Jun 13.

Nitrogen regulation of virulence in clinically prevalent fungal pathogens.

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  • 1School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Qld, Australia.


The habitats of fungal pathogens range from environmental to commensal, and the nutrient content of these different niches varies considerably. Upon infection of humans, nutrient availability changes significantly depending on the site and pathophysiology of infection. Nonetheless, a common feature enabling successful establishment in these niches is the ability to metabolise available nutrients including sources of nitrogen, carbon and essential metals such as iron. In particular, nitrogen source utilisation influences specific morphological transitions, sexual and asexual sporulation and virulence factor production. All these physiological changes confer selective advantages to facilitate fungal survival, proliferation and colonisation. The three most well-studied components of the nitrogen regulatory circuit that commonly impact fungal pathogenesis are the ammonium permeases (the nitrogen availability sensor candidate), ureases (a nitrogen-scavenging enzyme) and GATA transcription factors (global regulators of nitrogen catabolism). In certain species, the ammonium permease induces a morphological switch from yeast to invasive filamentous growth forms or infectious spores, while in others, urease is a bona fide virulence factor. In all species studied thus far, transcription of the ammonium permease and urease-encoding genes is modulated by GATA factors. Fungal pathogens therefore integrate the expression of different virulence-associated phenotypes into the regulatory network controlling nitrogen catabolism.

© 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.


Aspergillus fumigatus; Candida albicans; Coccidioides posadasii; Cryptococcus neoformans; Saccharomyces cerevisiae

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