Hydrogen cyanide as a biomarker for <i>Pseudomonas aeruginosa</i> in the breath of children with cystic fibrosis

Enderby, Beth; Smith, David; Carroll, Will; Lenney, Warren

doi:10.1002/ppul.20963

Cited by 135 publications

(160 citation statements)

References 30 publications

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“…There has been recent interest in using the cyanogenic properties of P. aeruginosa to develop a rapid method for its detection in CF patients (31,32). Although further work with a larger collection of strains is required, the reliability of this approach is brought into question by our findings.…”

Section: Discussioncontrasting

confidence: 51%

Strain-dependent diversity in the Pseudomonas aeruginosa quorum-sensing regulon

Chugani

Kim

Phattarasukol

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

101

115

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Quorum sensing allows bacteria to sense and respond to changes in population density. Acyl-homoserine lactones serve as quorumsensing signals for many Proteobacteria, and acyl-homoserine lactone signaling is known to control cooperative activities. Quorum-controlled activities vary from one species to another. Quorum-sensing controls a constellation of genes in the opportunistic pathogen Pseudomonas aeruginosa, which thrives in a number of habitats ranging from soil and water to animal hosts. We hypothesized that there would be significant variation in quorumsensing regulons among strains of P. aeruginosa isolated from different habitats and that differences in the quorum-sensing regulons might reveal insights about the ecology of P. aeruginosa. As a test of our hypothesis we used RNA-seq to identify quorumcontrolled genes in seven P. aeruginosa isolates of diverse origins. Although our approach certainly overlooks some quorum-sensingregulated genes we found a shared set of genes, i.e., a core quorum-controlled gene set, and we identified distinct, strain-variable sets of quorum-controlled genes, i.e., accessory genes. Some quorumcontrolled genes in some strains were not present in the genomes of other strains. We detected a correlation between traits encoded by some genes in the strain-variable subsets of the quorum regulons and the ecology of the isolates. These findings indicate a role for quorum sensing in extension of the range of habitats in which a species can thrive. This study also provides a framework for understanding the molecular mechanisms by which quorum-sensing systems operate, the evolutionary pressures by which they are maintained, and their importance in disparate ecological contexts.bacterial communication | systems biology | transcription control B acteria use quorum-sensing signals to communicate with each other and control gene expression in a cell density-dependent manner. Many species of Proteobacteria use diffusible acyl-homoserine lactones (AHLs) as quorum-sensing signals. AHLs are produced by signal synthase enzymes and are detected by signalspecific transcriptional regulators. AHL quorum-sensing circuits regulate a wide spectrum of phenotypes in a diverse array of α-, β-, and γ-Proteobacteria (1). Interspecies differences in quorum regulons often are a reflection of the diverse habitats that bacteria occupy, and quorum-controlled phenotypes often play a crucial role in niche persistence. The classic example is quorum control of luminescence in Vibrio fischeri, which allows this bacterium to discriminate between its free-living, low-populationdensity seawater habitat and its high-density symbiotic habitats, the light organs of certain fish and squid (2, 3). It is well established that there are species-specific differences in quorum regulons, but there is little information regarding the possibility of intraspecies strain-specific differences. We hypothesized that, particularly for versatile species that occupy diverse niches, there might be a shared core of quorum-controlled genes an...

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Section: Discussioncontrasting

confidence: 51%

Strain-dependent diversity in the Pseudomonas aeruginosa quorum-sensing regulon

Chugani

Kim

Phattarasukol

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

101

115

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“…The profile of exhaled VOCs in combination with multivariate analyses rather than single molecules [27] was found to be more informative for clinical diagnostics [28]. Despite the great potential of such a non-invasive diagnostic method, the technical issues are demanding [29] and breath sampling and VOCs extraction have to be further optimized.…”

Section: Discussionmentioning

confidence: 99%

A rapid method for breath analysis in cystic fibrosis patients

Kramer

Sauer-Heilborn

Welte

et al. 2014

Eur J Clin Microbiol Infect Dis

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Purpose: For easy handling and speed of lung diseases diagnostic, approaches based on volatile organic compounds (VOCs), including those emitted by pathogenic microorganisms, are considered but currently require considerable sampling efforts. We tested whether easy to handle and fast detection of lung infections is possible using Solid-Phase-Micro-Extraction (SPME) of 100 ml of exhaled breath. Methods: An analytical procedure for the detection of VOCs from the headspace of epithelial lung cells infected with four human pathogens was developed. The feasibility of this method was tested in a cystic fibrosis (CF) outpatient clinic in vivo. Exhaled breath was extracted by SPME and analyzed by gas chromatography-mass spectrometry. Results: The compositions of VOCs released in the infection model were characteristic for all individual pathogens tested.Exhaled breath of CF patients allowed clear distinction of CF patients and controls by their VOC compositions using multivariate analyses. Interestingly, the major specific VOCs detected in exhaled breath of infected CF patients in vivo differed from those monitored during bacterial in vitro growth. Conclusions: SPME extraction of VOCs from 100 ml of human breath allowed the distinction between CF patients and healthy probands. Our results highlight the importance of assessing the entire pattern of VOCs instead of selected biomarkers for diagnostic purposes, as well as the need for using clinical samples to identify reliable biomarkers. This study provides the proof-of-concept for the approach using the composition of exhaled VOCs in human breath for rapid identification of infectious agents in patients with lower respiratory tract infections.

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“…Cyanide has also been identified in the sputum [5,6] and HCN in the breath of CF and non-CF bronchiectasis patients infected with P. aeruginosa [5,7]. Conversely, cyanide is absent from the sputum of bronchiectasis patients without P. aeruginosa infection [5,6] and HCN is very low or absent from the breath of healthy children [8].…”

mentioning

confidence: 94%

“…This and the absence of cyanide from a small number of sputum/breath samples from P. aeruginosa infected patients [5][6][7] suggest that cyanide production is dependent on the presence of specific P. aeruginosa strains as well as the total P. aeruginosa load. This theory that cyanide production varies between P. aeruginosa genotypes is supported by the finding that the Liverpool epidemic P. aeruginosa strain overproduces certain quorum sensing regulated exoproducts such as LasA protease and elastase [19].…”

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confidence: 99%

“…The high P. aeruginosa population density of CF mucus maximises quorum-sensing cyanide production and together with its low O 2 concentration and ideal temperature, provides the perfect environmental parameters for P. aeruginosa cyanogenesis. The high concentrations of cyanide identified in the sputum and breath of CF patients [5][6][7] may well affect lung cellular function within human lungs, contributing to the long-term damage known to result from chronic P. aeruginosa infection. It may also assist P. aeruginosa in excluding other lung pathogens leading to it being the dominant bacterium.…”

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confidence: 99%

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