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Refinement of metabolite detection in cystic fibrosis sputum reveals heme negatively correlates with lung function

Glasser, Nathaniel R. and Hunter, Ryan C. and Liou, Theodore G. and Newman, Dianne K. (2018) Refinement of metabolite detection in cystic fibrosis sputum reveals heme negatively correlates with lung function. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20181128-093526010

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Abstract

Pseudomonas aeruginosa lung infections are a leading cause of morbidity and mortality in cystic fibrosis (CF) patients (1, 2). Our laboratory has studied a class of small molecules produced by P. aeruginosa known as phenazines, including pyocyanin and its biogenic precursor phenazine 1 carboxylic acid (PCA). As phenazines are known virulence factors (3), we and others have explored the possibility of using phenazine concentrations as a marker for disease progression (4, 5, 6). Previously, we reported that sputum concentrations of pyocyanin and PCA negatively correlate with lung function in cystic fibrosis patients (6). Our study used high performance liquid chromatography (HPLC) to quantify phenazines by UV vis absorbance after extraction from lung sputum. Since our initial study, methods for metabolite analysis have advanced considerably, aided in large part by usage of mass spectrometry (LC MS) and tandem mass spectrometry (LC MS/MS). Because a more recent study employing LC MS/MS revealed a surprising decoupling of P. aeruginosa metabolites in sputum and the detection of P. aeruginosa through culturing or microbiome profiles (4), we decided to check whether we could reproduce our previous findings by analyzing sputum samples from a different patient cohort with a new LC MS instrument in our laboratory. Our new samples were provided by the Mountain West CF Consortium Sputum Biomarker study (7). In the course of performing our new analyses, comparison of our old HPLC data to our new LC MS data led us to realize that the peak previously assigned to PCA instead originates from heme, and the peak assigned to pyocyanin originates from an as yet unknown compound. This correction only affects the measurements of phenazines in sputum, and we are confident in the phenazine measurements from isolated cultures and the 16S rRNA gene sequencing data from that study (6). Here we outline the basis for our correction and present additional data showing that heme concentration negatively correlates with lung function in cystic fibrosis patients.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/475525DOIDiscussion Paper
ORCID:
AuthorORCID
Newman, Dianne K.0000-0003-1647-1918
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license. The MWCFC Sputum Biomarker investigators included Frederick R Adler, Fadi Asfour, Barbara A Chatfield, Jessica A Francis, John R Hoidal, Judy L Jensen, Yanping Li, Theodore G Liou, Kristyn A Packer, Jane Vroom (University of Utah); Natalia Argel, Peggy Radford (Phoenix Children’s Hospital); Perry S Brown, Dixie Durham (St. Luke’s Cystic Fibrosis Center of Idaho); Cori L Daines, Osmara Molina (University of Arizona); Barbara Glover, Craig Nakamura, Ryan Yoshikawa (Cystic Fibrosis Center, Las Vegas); Theresa Heynekamp, Abby J Redway (University of New Mexico); Ruth Keogh (London School of Hygiene and Tropical Medicine); Carol M Kopecky, Scott D Sagel (Children's Hospital Colorado, University of Colorado School of Medicine); Noah Lechtzin (Johns Hopkins University School of Medicine); Jerimiah Lysinger, Shawna Sprandel (Montana Cystic Fibrosis Center, Billings Clinic); Katie R Poch, Jennifer L Taylor-Cousar (National Jewish Health); Alexandra L Quittner (Miami Children's Research Institute, Nicklaus Children's Hospital); John P Clancy (University of Cincinnati); J Stuart Elborn (Queen’s University, Belfast and Royal Brompton Hospital, London); Kenneth N Olivier (Laboratory of Chronic Airway Infection, Pulmonary Branch, National Heart Lung and Blood Institute, National Institutes of Health). We thank Dr. Nathan Dalleska at the Environmental Analysis Center (Caltech) for analytical support.
Record Number:CaltechAUTHORS:20181128-093526010
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20181128-093526010
Official Citation:Refinement of metabolite detection in cystic fibrosis sputum reveals heme negatively correlates with lung function Nathaniel R. Glasser, Ryan C. Hunter, Theodore G. Liou, Dianne K. K. Newman, Mountain West CF Consortium Investigators bioRxiv 475525; doi: https://doi.org/10.1101/475525
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:91271
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:28 Nov 2018 18:01
Last Modified:03 Oct 2019 20:33

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