Pseudomonas aeruginosa Volatilome Characteristics and Adaptations in Chronic Cystic Fibrosis Lung Infections

Trenton J. Davis, Ava V. Karanjia, Charity N. Bhebhe, Sarah B. West, Heather D. Bean, Trenton J. Davis, Heather D. Bean, Ava V. Karanjia, Matthew Richardson, Matthew Richardson

Research output: Contribution to journalArticlepeer-review

Abstract

Pseudomonas aeruginosa chronic lung infections in individuals with cys- tic fibrosis (CF) significantly reduce quality of life and increase morbidity and mortal-ity. Tracking these infections is critical for monitoring patient health and informing treatments. We are working toward the development of novel breath-based bio-markers to track chronic P. aeruginosa lung infections in situ. Using comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC×GC-TOF-MS), we characterized the in vitro volatile metabolomes (“volatilomes”) of 81 P. aeruginosa isolates collected from 17 CF patients over at least a 5-year pe-riod of their chronic lung infections. We detected 539 volatiles produced by the P. aeruginosa isolates, 69 of which were core volatiles that were highly conserved. We found that each early infection isolate has a unique volatilome, and as infection pro-gresses, the volatilomes of isolates from the same patient become increasingly dis-similar, to the point that these intrapatient isolates are no more similar to one an-other than to isolates from other patients. We observed that the size and chemical diversity of P. aeruginosa volatilomes do not change over the course of chronic in-fections; however, the relative abundances of core hydrocarbons, alcohols, and alde-hydes do change and are correlated with changes in phenotypes associated with chronic infections. This study indicates that it may be feasible to track P. aeruginosa chronic lung infections by measuring changes to the infection volatilome and lays the groundwork for exploring the translatability of this approach to direct measure-ment using patient breath. IMPORTANCE Pseudomonas aeruginosa is a leading cause of chronic lung infections in cystic fibrosis (CF), which are correlated with lung function decline. Significant clinical efforts are therefore aimed at detecting infections and tracking them for phenotypic changes, such as mucoidy and antibiotic resistance. Both the detection and tracking of lung infections rely on sputum cultures, but due to improvements in CF therapies, sputum production is declining, although risks for lung infections persist. Therefore, we are working toward the development of breath-based di-agnostics for CF lung infections. In this study, we characterized of the volatile metabolomes of 81 P. aeruginosa clinical isolates collected from 17 CF patients over a duration of at least 5 years of a chronic lung infection. We found that the volatilome of P. aeruginosa adapts over time and is correlated with infection phenotype changes, suggesting that it may be possible to track chronic CF lung infections with a breath test.

Original languageEnglish (US)
Article numbere00843-20
Pages (from-to)1-19
Number of pages19
JournalmSphere
Volume5
Issue number5
DOIs
StatePublished - Jan 1 2020

Keywords

  • Pseudomonas aeruginosa
  • adaptation
  • biomarkers
  • chronic infection
  • cystic fibrosis
  • metabolomics
  • volatile organic compounds

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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