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Pediatric Cystic Fibrosis Sputum Can Be Chemically Dynamic, Anoxic, and Extremely Reduced Due to Hydrogen Sulfide Formation

Cowley, Elise S. and Kopf, Sebastian H. and LaRiviere, Alejandro and Ziebis, Wiebke and Newman, Dianne K. (2015) Pediatric Cystic Fibrosis Sputum Can Be Chemically Dynamic, Anoxic, and Extremely Reduced Due to Hydrogen Sulfide Formation. mBio, 6 (4). Art. No. e00767. ISSN 2150-7511. PMCID PMC4551978. http://resolver.caltech.edu/CaltechAUTHORS:20151002-111813971

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Abstract

Severe and persistent bacterial lung infections characterize cystic fibrosis (CF). While several studies have documented the microbial diversity within CF lung mucus, we know much less about the inorganic chemistry that constrains microbial metabolic processes and their distribution. We hypothesized that sputum is chemically heterogeneous both within and between patients. To test this, we measured microprofiles of oxygen and sulfide concentrations as well as pH and oxidation-reduction potentials in 48 sputum samples from 22 pediatric patients with CF. Inorganic ions were measured in 20 samples from 12 patients. In all cases, oxygen was depleted within the first few millimeters below the sputum-air interface. Apart from this steep oxycline, anoxia dominated the sputum environment. Different sputum samples exhibited a broad range of redox conditions, with either oxidizing (16 mV to 355 mV) or reducing (−300 to −107 mV) potentials. The majority of reduced samples contained hydrogen sulfide and had a low pH (2.9 to 6.5). Sulfide concentrations increased at a rate of 0.30 µM H_2S/min. Nitrous oxide was detected in only one sample that also contained sulfide. Microenvironmental variability was observed both within a single patient over time and between patients. Modeling oxygen dynamics within CF mucus plugs indicates that anoxic zones vary as a function of bacterial load and mucus thickness and can occupy a significant portion of the mucus volume. Thus, aerobic respiration accounts only partially for pathogen survival in CF sputum, motivating research to identify mechanisms of survival under conditions that span fluctuating redox states, including sulfidic environments.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1128/mBio.00767-15DOIArticle
http://mbio.asm.org/content/6/4/e00767-15PublisherArticle
http://mbio.asm.org/content/suppl/2015/07/27/mBio.00767-15.DCSupplementalPublisherSupplemental Material
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4551978/PubMed CentralArticle
ORCID:
AuthorORCID
Newman, Dianne K.0000-0003-1647-1918
Additional Information:© 2015 Cowley et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. Received 7 May 2015; Accepted 25 June 2015; Published 28 July 2015. This work was supported by NIH grant R01HL117328 and the Howard Hughes Medical Institute (HHMI). D.K.N. is an HHMI Investigator. We thank Roberta Kato, Kyle McCallin, Carmen Reyes, and the entire pulmonary clinic team at Children’s Hospital, Los Angeles, CA, for their support; Nathan Dalleska and the Caltech Environmental Analysis Center for instrumentation that benefitted this study; Chris Kempes for modeling advice; and members of the Newman laboratory and Unisense A/S for constructive feedback throughout this project.
Funders:
Funding AgencyGrant Number
NIHR01HL117328
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
PubMed Central ID:PMC4551978
Record Number:CaltechAUTHORS:20151002-111813971
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20151002-111813971
Official Citation:Cowley ES, Kopf SH, LaRiviere A, Ziebis W, Newman DK. 2015. Pediatric cystic fibrosis sputum can be chemically dynamic, anoxic, and extremely reduced due to hydrogen sulfide formation. mBio 6(4):e00767-15. doi:10.1128/mBio.00767-15
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:60704
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:02 Oct 2015 18:33
Last Modified:24 Oct 2017 16:37

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