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Phenazine-1-Carboxylic Acid Promotes Bacterial Biofilm Development via Ferrous Iron Acquisition

Wang, Yun and Wilks, Jessica C. and Danhorn, Thomas and Ramos, Itzel and Croal, Laura R. and Newman, Dianne K. (2011) Phenazine-1-Carboxylic Acid Promotes Bacterial Biofilm Development via Ferrous Iron Acquisition. Journal of Bacteriology, 193 (14). pp. 3606-3617. ISSN 0021-9193. PMCID PMC3133341.

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The opportunistic pathogen Pseudomonas aeruginosa forms biofilms, which render it more resistant to antimicrobial agents. Levels of iron in excess of what is required for planktonic growth have been shown to promote biofilm formation, and therapies that interfere with ferric iron [Fe(III)] uptake combined with antibiotics may help treat P. aeruginosa infections. However, use of these therapies presumes that iron is in the Fe(III) state in the context of infection. Here we report the ability of phenazine-1-carboxylic acid (PCA), a common phenazine made by all phenazine-producing pseudomonads, to help P. aeruginosa alleviate Fe(III) limitation by reducing Fe(III) to ferrous iron [Fe(II)]. In the presence of PCA, a P. aeruginosa mutant lacking the ability to produce the siderophores pyoverdine and pyochelin can still develop into a biofilm. As has been previously reported (P. K. Singh, M. R. Parsek, E. P. Greenberg, and M. J. Welsh, Nature 417:552-555, 2002), biofilm formation by the wild type is blocked by subinhibitory concentrations of the Fe(III)-binding innate-immunity protein conalbumin, but here we show that this blockage can be rescued by PCA. FeoB, an Fe(II) uptake protein, is required for PCA to enable this rescue. Unlike PCA, the phenazine pyocyanin (PYO) can facilitate biofilm formation via an iron-independent pathway. While siderophore-mediated Fe(III) uptake is undoubtedly important at early stages of infection, these results suggest that at later stages of infection, PCA present in infected tissues may shift the redox equilibrium between Fe(III) and Fe(II), thereby making iron more bioavailable.

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Newman, Dianne K.0000-0003-1647-1918
Additional Information:© 2011 American Society for Microbiology. Received 23 March 2011; Accepted 9 May 2011. Published ahead of print on 20 May 2011. We thank N. C. Caiazza and L. E. P. Dietrich for assistance with mutagenesis; I. J. Schalk, G. L. A. Mislin, and F. Hoegy for the gifts of pyoverdine and pyochelin; and L. E. P. Dietrich, Alexa Price-Whelan, and the anonymous reviewers for constructive feedback. This work was supported by grants to D.K.N. from the Packard Foundation and the Howard Hughes Medical Institute and an NSF graduate research fellowship to J.C.W. D.K.N. is an Investigator of the Howard Hughes Medical Institute.
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Packard FoundationUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
NSF Graduate Research FellowshipUNSPECIFIED
Issue or Number:14
PubMed Central ID:PMC3133341
Record Number:CaltechAUTHORS:20130403-141504385
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:37746
Deposited By: Jason Perez
Deposited On:04 Apr 2013 15:04
Last Modified:03 Oct 2019 04:50

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