Levels of amino acids and related compounds in bronchoalveolar lavage fluids of asthmatic patients.

Hofford, James M.; Milakofsky, Louis; Pell, Sidney; Fish, James E.; Peters, S. P.; Pollice, Mary; Vogel, Wolfgang

doi:10.1164/ajrccm.155.2.9032174

Cited by 18 publications

(18 citation statements)

References 14 publications

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“…Taurine is a cysteine-derived sulfonic acid that has been shown to be highly concentrated in the bronchoalveolar lavage fluid of both healthy and asthmatic patients (37). This compound can be used as a sulfur source by many bacterial and fungal species, including A. fumigatus (33).…”

Section: Resultsmentioning

confidence: 99%

“…This suggests that there might be a pool of free sulfate in the extracellular matrix (35), pointing to this inorganic compound as a putative S source. Moreover, tissue free S-containing amino acids (methionine, cysteine, and taurine) have been detected in human lungs (36), and taurine has been shown to be highly concentrated in the bronchoalveolar lavage fluid of both healthy and asthmatic patients (37). Therefore, we scrutinized the fungal transsulfuration pathway by generating and characterizing various A. fumigatus mutants impaired in the utilization of different S sources.…”

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confidence: 99%

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Exploration of Sulfur Assimilation of Aspergillus fumigatus Reveals Biosynthesis of Sulfur-Containing Amino Acids as a Virulence Determinant

et al. 2016

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e Fungal infections are of major relevance due to the increased numbers of immunocompromised patients, frequently delayed diagnosis, and limited therapeutics. To date, the growth and nutritional requirements of fungi during infection, which are relevant for invasion of the host, are poorly understood. This is particularly true for invasive pulmonary aspergillosis, as so far, sources of (macro)elements that are exploited during infection have been identified to only a limited extent. Here, we have investigated sulfur (S) utilization by the human-pathogenic mold Aspergillus fumigatus during invasive growth. Our data reveal that inorganic S compounds or taurine is unlikely to serve as an S source during invasive pulmonary aspergillosis since a sulfate transporter mutant strain and a sulfite reductase mutant strain are fully virulent. In contrast, the S-containing amino acid cysteine is limiting for fungal growth, as proven by the reduced virulence of a cysteine auxotroph. Moreover, phenotypic characterization of this strain further revealed the robustness of the subordinate glutathione redox system. Interestingly, we demonstrate that methionine synthase is essential for A. fumigatus virulence, defining the biosynthetic route of this proteinogenic amino acid as a potential antifungal target. In conclusion, we provide novel insights into the nutritional requirements of A. fumigatus during pathogenesis, a prerequisite to understanding and fighting infection.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Exploration of Sulfur Assimilation of Aspergillus fumigatus Reveals Biosynthesis of Sulfur-Containing Amino Acids as a Virulence Determinant

et al. 2016

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“…The mechanism of increase in plasma taurine can only be speculated because of lack of any data in the literature in relation to asthma. Taurine levels have been reported to be higher in the bronchoalveolar lavage (BAL) fluid of individuals with asthma (20, 21). Whether the increase the levels of taurine in BAL is related to higher NO or other cytokines in asthma or are a result of release from damaged cells has not been examined.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic Endotype of Asthma

Comhair

McDunn

Bennett

et al. 2015

The Journal of Immunology

115

123

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Metabolomics, the quantification of small biochemicals in plasma and tissues, can provide insight into complex biochemical processes and enable the identification of biomarkers that may serve as therapeutic targets. We hypothesized that the plasma metabolome of asthma would reveal metabolic consequences of the specific immune and inflammatory responses unique to endotypes of asthma. The plasma metabolomic profiles of 20 asthmatic subjects and 10 healthy controls were examined using an untargeted global and focused metabolomic analysis. Individuals were classified based upon clinical definitions of asthma severity or by levels of fraction of exhaled nitric oxide (FENO), a biomarker of airway inflammation. Of the 293 biochemicals identified in the plasma, 25 were significantly different among asthma and healthy controls (p<0.05). Plasma levels of taurine, lathosterol, bile acids (taurocholate and glycodeoxycholate), nicotinamide, and adenosine-5-phosphate, were significantly higher in asthmatics compared with healthy controls. Severe asthmatics had biochemical changes related to steroid and amino acid/protein metabolism. Asthmatics with high FENO, compared with those with low FENO, had higher levels of plasma branched chain amino acids and bile acids. Asthmatics have a unique plasma metabolome that distinguishes them from healthy controls and points to activation of inflammatory and immune pathways. The severe asthmatic and high FENO asthmatic have unique endotypes that suggest changes in NO-associated taurine transport and bile acid metabolism.

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“…Levels of taurine were measured in human airways. 27 It is reported to have a role in airway smooth muscle relaxation 28 and appears to correlate with airway neutrophilia. 29 There is also a reported link between increased inflammation, oxidative stress, and high taurine levels.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic profiling of asthma and chronic obstructive pulmonary disease: A pilot study differentiating diseases

Adamko

Nair

Mayers

et al. 2015

Journal of Allergy and Clinical Immunology

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Levels of amino acids and related compounds in bronchoalveolar lavage fluids of asthmatic patients.

Cited by 18 publications

References 14 publications

Exploration of Sulfur Assimilation of Aspergillus fumigatus Reveals Biosynthesis of Sulfur-Containing Amino Acids as a Virulence Determinant

Exploration of Sulfur Assimilation of Aspergillus fumigatus Reveals Biosynthesis of Sulfur-Containing Amino Acids as a Virulence Determinant

Metabolomic Endotype of Asthma

Metabolomic profiling of asthma and chronic obstructive pulmonary disease: A pilot study differentiating diseases

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