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11 01, 2021;11 (1): 21419.

Metabolomic profiling of Burkholderia cenocepacia in synthetic cystic fibrosis sputum medium reveals nutrient environment-specific production of virulence factors.

Olakunle A Jaiyesimi, Andrew C McAvoy, David N Fogg, Neha Garg
Author Information
  1. Olakunle A Jaiyesimi: School of Chemistry and Biochemistry, Georgia Institute of Technology, 950 Atlantic Drive, Atlanta, GA, 30332-2000, USA.
  2. Andrew C McAvoy: School of Chemistry and Biochemistry, Georgia Institute of Technology, 950 Atlantic Drive, Atlanta, GA, 30332-2000, USA.
  3. David N Fogg: School of Chemistry and Biochemistry, Georgia Institute of Technology, 950 Atlantic Drive, Atlanta, GA, 30332-2000, USA.
  4. Neha Garg: School of Chemistry and Biochemistry, Georgia Institute of Technology, 950 Atlantic Drive, Atlanta, GA, 30332-2000, USA. neha.garg@chemistry.gatech.edu.
PMID: 34725378 DOI: 10.1038/s41598-021-00421-4

Abstract

Infections by Burkholderia cenocepacia lead to life-threatening disease in immunocompromised individuals, including those living with cystic fibrosis (CF). While genetic variation in various B. cenocepacia strains has been reported, it remains unclear how the chemical environment of CF lung influences the production of small molecule virulence factors by these strains. Here we compare metabolomes of three clinical B. cenocepacia strains in synthetic CF sputum medium (SCFM2) and in a routine laboratory medium (LB), in the presence and absence of the antibiotic trimethoprim. Using a mass spectrometry-based untargeted metabolomics approach, we identify several compound classes which are differentially produced in SCFM2 compared to LB media, including siderophores, antimicrobials, quorum sensing signals, and various lipids. Furthermore, we describe that specific metabolites are induced in the presence of the antibiotic trimethoprim only in SCFM2 when compared to LB. Herein, C13-acyl-homoserine lactone, a quorum sensing signal previously not known to be produced by B. cenocepacia as well as pyochelin-type siderophores were exclusively detected during growth in SCFM2 in the presence of trimethoprim. The comparative metabolomics approach described in this study provides insight into environment-dependent production of secondary metabolites by B. cenocepacia strains and suggests future work which could identify personalized strain-specific regulatory mechanisms involved in production of secondary metabolites. Investigations into whether antibiotics with different mechanisms of action induce similar metabolic alterations will inform development of combination treatments aimed at effective clearance of Burkholderia spp. pathogens.

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MeSH Term

Anti-Bacterial Agents
Bacterial Proteins
Burkholderia Infections
Burkholderia cenocepacia
Chromatography, High Pressure Liquid
Culture Media
Cystic Fibrosis
Humans
Lipids
Metabolome
Metabolomics
Microbial Sensitivity Tests
Quorum Sensing
Sputum
Trimethoprim
Virulence Factors

Chemicals

Anti-Bacterial Agents
Bacterial Proteins
Culture Media
Lipids
Virulence Factors
Trimethoprim
Journal Article
Article has an altmetric score of 2

Word Cloud

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