title: Breath gas metabolites and bacterial metagenomes from cystic fibrosis airways indicate active pH neutral 2,3-butanedione fermentation.
abstract: The airways of cystic fibrosis (CF) patients are chronically colonized by patient-specific polymicrobial communities. The conditions and nutrients available in CF lungs affect the physiology and composition of the colonizing microbes. Recent work in bioreactors has shown that the fermentation product 2,3-butanediol mediates cross-feeding between some fermenting bacteria and Pseudomonas aeruginosa, and that this mechanism increases bacterial current production. To examine bacterial fermentation in the respiratory tract, breath gas metabolites were measured and several metagenomes were sequenced from CF and non-CF volunteers. 2,3-butanedione was produced in nearly all respiratory tracts. Elevated levels in one patient decreased during antibiotic treatment, and breath concentrations varied between CF patients at the same time point. Some patients had high enough levels of 2,3-butanedione to irreversibly damage lung tissue. Antibiotic therapy likely dictates the activities of 2,3-butanedione-producing microbes, which suggests a need for further study with larger sample size. Sputum microbiomes were dominated by P. aeruginosa, Streptococcus spp. and Rothia mucilaginosa, and revealed the potential for 2,3-butanedione biosynthesis. Genes encoding 2,3-butanedione biosynthesis were disproportionately abundant in Streptococcus spp, whereas genes for consumption of butanedione pathway products were encoded by P. aeruginosa and R. mucilaginosa. We propose a model where low oxygen conditions in CF lung lead to fermentation and a decrease in pH, triggering 2,3-butanedione fermentation to avoid lethal acidification. We hypothesize that this may also increase phenazine production by P. aeruginosa, increasing reactive oxygen species and providing additional electron acceptors to CF microbes.
authors.affiliation: Department of Biology, San Diego State University, San Diego, CA, USA.
authors.forename: Katrine L
authors.initials: KL
authors.lastname: Whiteson
authors.affiliation: Department of Chemistry, University of California, Irvine, CA, USA.
authors.forename: Simone
authors.initials: S
authors.lastname: Meinardi
authors.affiliation: Department of Biology, San Diego State University, San Diego, CA, USA.
authors.forename: Yan Wei
authors.initials: YW
authors.lastname: Lim
authors.affiliation: Department of Biology, San Diego State University, San Diego, CA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Schmieder
authors.affiliation: Ronin Institute, Montclair, NJ, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Maughan
authors.affiliation: Department of Biology, San Diego State University, San Diego, CA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Quinn
authors.affiliation: Department of Chemistry, University of California, Irvine, CA, USA.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Blake
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Conrad
authors.affiliation: Department of Biology, San Diego State University, San Diego, CA, USA.
authors.forename: Forest
authors.initials: F
authors.lastname: Rohwer
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001944:Breath Tests; D002072:Butylene Glycols / Q000378:metabolism; D060085:Coinfection / Q000188:drug therapy / Q000382:microbiology*; D003550:Cystic Fibrosis / Q000150:complications*; D003931:Diacetyl / Q000378:metabolism*; D005285:Fermentation; D016680:Genome, Bacterial; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D054892:Metagenome; D013183:Sputum / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D002072:Butylene Glycols; C026978:2,3-butylene glycol; D003931:Diacetyl