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Geisel School of Medicine


Candidaalbicanshasdevelopmentalprogramsthatgoverntransitionsbetweenyeastandfilamentousmorphologies and between unattached and biofilm lifestyles. Here, we report that filamentation, intercellular adherence, and biofilm develop- ment were inhibited during interactions between Candida albicans and Pseudomonas aeruginosa through the action of P. aeruginosa-produced phenazines. While phenazines are toxic to C. albicans at millimolar concentrations, we found that lower concentrations of any of three different phenazines (pyocyanin, phenazine methosulfate, and phenazine-1-carboxylate) allowed growth but affected the development of C. albicans wrinkled colony biofilms and inhibited the fungal yeast-to-filament transition. Phenazines impaired C. albicans growth on nonfermentable carbon sources and led to increased production of fer- mentation products (ethanol, glycerol, and acetate) in glucose-containing medium, leading us to propose that phenazines specif- ically inhibited respiration. Methylene blue, another inhibitor of respiration, also prevented the formation of structured colony biofilms. The inhibition of filamentation and colony wrinkling was not solely due to lowered extracellular pH induced by fer- mentation. Compared to smooth, unstructured colonies, wrinkled colony biofilms had higher oxygen concentrations within the colony, and wrinkled regions of these colonies had higher levels of respiration. Together, our data suggest that the structure of the fungal biofilm promotes access to oxygen and enhances respiratory metabolism and that the perturbation of respiration by bacterial molecules such as phenazines or compounds with similar activities disrupts these pathways. These findings may sug- gest new ways to limit fungal biofilms in the context of disease.



Original Citation

Morales DK, Grahl N, Okegbe C, Dietrich LE, Jacobs NJ, Hogan DA. Control of Candida albicans metabolism and biofilm formation by Pseudomonas aeruginosa phenazines. mBio. 2013 Jan 29;4(1):e00526-12. doi: 10.1128/mBio.00526-12. PMID: 23362320; PMCID: PMC3560528.