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Neutrophil elastase correlates with increased sphingolipid content in cystic fibrosis sputum.

ABSTRACT: INTRODUCTION:Sphingolipids are associated with the regulation of pulmonary inflammation. Although sphingolipids have been investigated in the context of cystic fibrosis (CF), the focus has been on loss of CF transmembrane conductance regulator (CFTR) function in mice, and in CF human lung epithelial cell lines. The sphingolipid content of CF sputum and the potential link between ceramide and airway inflammation in CF remain relatively unexplored. METHODS:Fifteen patients with CF provided two spontaneously expectorated sputum samples, one collected during a hospitalization for an acute pulmonary exacerbation and one from an outpatient visit at a time of clinical stability. Sputum was processed, and the supernatant assessed for active neutrophil elastase (NE) using a chromogenic microplate assay and sphingolipid content using reverse phase high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Relevant demographic data including age, sex, CF genotype, FEV1 % predicted, and sputum bacteriology were assessed as possible modifying factors that could influence the correlation between NE and sputum sphingolipids. Data were analyzed for linear correlation, with statistical significance pre-defined as P?

SUBMITTER: Karandashova S

PROVIDER: S-EPMC6566867 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Neutrophil elastase correlates with increased sphingolipid content in cystic fibrosis sputum.

Karandashova Sophia S Kummarapurugu Apparao A Zheng Shuo S Kang Le L Sun Shumei S Rubin Bruce K BK Voynow Judith A JA

Pediatric pulmonology 20180406 7

<h4>Introduction</h4>Sphingolipids are associated with the regulation of pulmonary inflammation. Although sphingolipids have been investigated in the context of cystic fibrosis (CF), the focus has been on loss of CF transmembrane conductance regulator (CFTR) function in mice, and in CF human lung epithelial cell lines. The sphingolipid content of CF sputum and the potential link between ceramide and airway inflammation in CF remain relatively unexplored.<h4>Methods</h4>Fifteen patients with CF p ...[more]

PMID: 29624923

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Project description:Stenotrophomonas maltophilia is a Gram-negative opportunistic pathogen that can infect the lungs of people with cystic fibrosis (CF). The highly viscous mucus in the CF lung, expectorated as sputum, serves as the primary nutrient source for microbes colonizing this site and induces virulence-associated phenotypes and gene expression in several CF pathogens. Here, we characterized the transcriptional responses of three S. maltophilia strains during exposure to synthetic CF sputum medium (SCFM2) to gain insight into how this organism interacts with the host in the CF lung. These efforts led to the identification of 881 transcripts differentially expressed by all three strains, many of which reflect the metabolic pathways used by S. maltophilia in sputum, as well as altered stress responses. The latter correlated with increased resistance to peroxide exposure after pregrowth in SCFM2 for two of the strains. We also compared the SCFM2 transcriptomes of two S. maltophilia CF isolates to that of the acute infection strain, S. maltophilia K279a, allowing us to identify CF isolate-specific signatures in differential gene expression. The expression of genes from the accessory genomes was also differentially altered in response to SCFM2. Finally, a number of biofilm-associated genes were differentially induced in SCFM2, particularly in K279a, which corresponded to increased aggregation and biofilm formation in this strain relative to both CF strains. Collectively, this work details the response of S. maltophilia to an environment that mimics important aspects of the CF lung, identifying potential survival strategies and metabolic pathways used by S. maltophilia during infections.IMPORTANCEStenotrophomonas maltophilia is an important infecting bacterium in the airways of people with cystic fibrosis (CF). However, compared to the other CF pathogens, S. maltophilia has been relatively understudied. The significance of our research is to provide insight into the global transcriptomic changes of S. maltophilia in response to a medium that was designed to mimic important aspects of the CF lung. This study elucidates the overall metabolic changes that occur when S. maltophilia encounters the CF lung and generates a road map of candidate genes to test using in vitro and in vivo models of CF.

Dataset Information

Neutrophil elastase correlates with increased sphingolipid content in cystic fibrosis sputum.

Publications

Neutrophil elastase correlates with increased sphingolipid content in cystic fibrosis sputum.

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