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Phenazine Content in the Cystic Fibrosis Respiratory Tract Negatively Correlates with Lung Function and Microbial Complexity

Hunter, Ryan C. and Klepac-Ceraj, Vanja and Lorenzi, Magen M. and Grotzinger, Hannah and Martin, Thomas R. and Newman, Dianne K. (2012) Phenazine Content in the Cystic Fibrosis Respiratory Tract Negatively Correlates with Lung Function and Microbial Complexity. American Journal of Respiratory Cell and Molecular Biology, 47 (6). pp. 738-745. ISSN 1044-1549.

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Although much is known about how virulence factors affect pathogens and host tissues in vitro, far less is understood about their dynamics in vivo. As a step toward characterizing the chemistry of infected environments, we measured phenazine abundance in the lungs of patients with cystic fibrosis (CF). Phenazines are redox-active small molecules produced by Pseudomonas aeruginosa that damage host epithelia, curb the growth of competing organisms, and play physiologically important roles in the cells that produce them. Here, we quantify phenazines within expectorated sputum, characterize the P. aeruginosa populations responsible for phenazine production, and assess their relationship to CF lung microflora. Chemical analyses of expectorated sputum showed that the concentrations of two phenazines, namely, pyocyanin (PYO) and phenazine-1–carboxylic acid (PCA), were negatively correlated (ρ = −0.68 and −0.57, respectively) with lung function. Furthermore, the highest phenazine concentrations were found in patients whose pulmonary function showed the greatest rates of decline. The constituent P. aeruginosa populations within each patient showed diverse capacities for phenazine production. Early during infection, individual isolates produced more PYO than later during infection. However, total PYO concentrations in sputum at any given stage correlated well with the average production by the total P. aeruginosa population. Finally, bacterial community complexity was negatively correlated with phenazine concentrations and declines in lung function, suggesting a link to the refinement of the overall microbial population. Together, these data demonstrate that phenazines negatively correlate with CF disease states in ways that were previously unknown, and underscore the importance of defining in vivo environmental parameters to better predict clinical outcomes of infections.

Item Type:Article
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URLURL TypeDescription
Hunter, Ryan C.0000-0003-3841-1676
Newman, Dianne K.0000-0003-1647-1918
Additional Information:© 2012 by the American Thoracic Society. Received in original form March 4, 2012 and in final form July 24, 2012. Published ahead of print on August 2012. This work was supported by the Howard Hughes Medical Institute (D.K.N.); by the Canadian Cystic Fibrosis Foundation (R.C.H); and by a grant from the Cystic Fibrosis Foundation Center to Children’s Hospital Boston for the sequencing of samples. The authors thank the individuals who participated in this study, and Erin Leone and Chao-Yu Guo for data collection and experimental design. The authors also thank Maureen Coleman and other members of the Newman Laboratory, California Institute of Technology, for critically reviewing the manuscript. The Committee on Clinical Investigation, CHLA, approved this study (protocol 09-04-0183).
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Canadian Cystic Fibrosis FoundationUNSPECIFIED
Subject Keywords:phenazine; cystic fibrosis; Pseudomonas aeruginosa; biofilm; microbiome
Issue or Number:6
Record Number:CaltechAUTHORS:20121210-081645386
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Official Citation: Ryan C. Hunter, Vanja Klepac-Ceraj, Magen M. Lorenzi, Hannah Grotzinger, Thomas R. Martin, and Dianne K. Newman Phenazine Content in the Cystic Fibrosis Respiratory Tract Negatively Correlates with Lung Function and Microbial Complexity Am. J. Respir. Cell Mol. Biol. 2012; 47: 738-745. First published online August 3, 2012 as doi:10.1165/rcmb.2012-0088OC
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:35889
Deposited By: Ruth Sustaita
Deposited On:10 Dec 2012 17:35
Last Modified:09 Mar 2020 13:18

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