Biosignificance of bacterial cyanogenesis in the CF lung

Anderson, R.; Roddam, Louise F.; Bettiol, SS; Sanderson, K; Reid, David W.

doi:10.1016/j.jcf.2009.12.003

Cited by 34 publications

(37 citation statements)

References 71 publications

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“…Cyanide is released intracellularly and is rapidly cleared and cyanide toxicity is not expected. While elevated pulmonary secretion cyanide levels have been reported in CF, these likely result from Pseudomonas and Burkholderia secretions 32 . In the current study, only one of seven subjects had a detectable cyanide level, and this was within the laboratory reference range.…”

Section: Discussionmentioning

confidence: 95%

Vitamin B₁₂ Status in Children With Cystic Fibrosis and Pancreatic Insufficiency

Maqbool

Schall²,

Mascarenhas³

et al. 2014

J. pediatr. gastroenterol. nutr.

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Objective Unexpectedly high serum B12 concentrations were noted in most study subjects with cystic fibrosis (CF) and pancreatic insufficiency (PI) participating in a nutrition intervention at the baseline evaluation. The objectives of this study were to determine dietary, supplement-based and enzyme-based B12 intake, serum B12 concentrations, and predictors of vitamin B12 status in children with CF and PI. Study Design Serum B12 status was assessed in subjects (5-18 yrs) and categorized as elevated (Hi-B12) or within reference range (RR-B12) for age and sex. Serum homocysteine, plasma B6, red blood cell folate, height, weight, and body mass index Z scores, pulmonary function, energy, dietary and supplement-based vitamin intake were assessed. Results 106 subjects, mean age 10.4 ± 3.0 years participated. Median serum B12 was 1083 pg/ml, with 56% in the Hi-B12 group. Dietary and supplement-based B12 intake were both high representing 376% and 667% Recommended Dietary Allowance (RDA). The Hi-B12 group had significantly greater supplement-based B12 intake than the RR-B12 group (1000 vs. 583% RDA, p<0.001). By multiple logistic regression analysis, high supplement-based B12 intake and age >12 years increased risk for Hi-B12, while higher FEV1 decreased risk (Pseudo-R2=0.18, P<0.001). Conclusions Serum B12 was elevated in the majority of children with CF and PI. Supplement-based B12 intake was 6 to 10 times the RDA, and strongly predicted elevated serum B12 status. The health consequences of lifelong high supplement-based B12 intake and high serum B12 are unknown and require further study, as does the inversed correlation between serum B12 and FEV1.

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Section: Discussionmentioning

confidence: 95%

Vitamin B₁₂ Status in Children With Cystic Fibrosis and Pancreatic Insufficiency

Maqbool

Schall²,

Mascarenhas³

et al. 2014

J. pediatr. gastroenterol. nutr.

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“…aeruginosa produces cyanide under low-oxygen conditions (16). Cyanogenesis is believed to contribute to the virulence of P. aeruginosa by suppressing the growth of other microorganisms infected in the same niches and by killing the host cells (24). The Pseudomonas species that carry the ccoN4-type genes were found to carry hcn genes involved in the biosynthesis of cyanide (25) (Fig.…”

Section: Discussionmentioning

confidence: 99%

Expression of multiplecbb₃cytochromecoxidase isoforms by combinations of multiple isosubunits inPseudomonas aeruginosa

Hirai

Osamura

Ishii

et al. 2016

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

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The ubiquitous opportunistic human pathogen Pseudomonas aeruginosa has five terminal oxidases for aerobic respiration and uses them under different growth conditions. Two of them are cbb 3 -type cytochrome c oxidases encoded by the gene clusters ccoN1O1Q1P1 and ccoN2O2Q2P2, which are the main terminal oxidases under high-and low-oxygen conditions, respectively. P. aeruginosa also has two orphan gene clusters, ccoN3Q3 and ccoN4Q4, encoding the core catalytic CcoN isosubunits, but the roles of these genes have not been clarified. We found that 16 active cbb 3 isoforms could be produced by combinations of four CcoN, two CcoO, and two CcoP isosubunits. The CcoN3-or CcoN4-containing isoforms were produced in the WT cell membrane in response to nitrite and cyanide, respectively. The strains carrying these isoforms were more resistant to nitrite or cyanide under low-oxygen conditions. These results indicate that P. aeruginosa gains resistance to respiratory inhibitors using multiple cbb 3 isoforms with different features, which are produced through exchanges of multiple core catalytic isosubunits.

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“…The potential clinical significance of cyanide in CF lung infections was recently demonstrated by the detection of cyanide in sputum from cystic fibrosis patients infected with P. aeruginosa and its presence is associated with a decline in lung function [8], [9]. However, the clinical significance of cyanogenesis and its consequences for the host remain unclear [10], [11]. Cyanide is volatile and its usefulness as a surrogate marker for the diagnosis of P. aeruginosa and Bcc infection in children who cannot expectorate sputum is currently being investigated [12], [13].…”

Section: Introductionmentioning

confidence: 99%

The Mucoid Switch in Pseudomonas aeruginosa Represses Quorum Sensing Systems and Leads to Complex Changes to Stationary Phase Virulence Factor Regulation

et al. 2014

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The opportunistic pathogen Pseudomonas aeruginosa chronically infects the airways of Cystic Fibrosis (CF) patients during which it adapts and undergoes clonal expansion within the lung. It commonly acquires inactivating mutations of the anti-sigma factor MucA leading to a mucoid phenotype, caused by excessive production of the extracellular polysaccharide alginate that is associated with a decline in lung function. Alginate production is believed to be the key benefit of mucA mutations to the bacterium in the CF lung. A phenotypic and gene expression characterisation of the stationary phase physiology of mucA22 mutants demonstrated complex and subtle changes in virulence factor production, including cyanide and pyocyanin, that results in their down-regulation upon entry into stationary phase but, (and in contrast to wildtype strains) continued production in prolonged stationary phase. These findings may have consequences for chronic infection if mucoid P. aeruginosa were to continue to make virulence factors under non-growing conditions during infection. These changes resulted in part from a severe down-regulation of both AHL-and AQ (PQS)-dependent quorum sensing systems. In trans expression of the cAMP-dependent transcription factor Vfr restored both quorum sensing defects and virulence factor production in early stationary phase. Our findings have implications for understanding the evolution of P. aeruginosa during CF lung infection and it demonstrates that mucA22 mutation provides a second mechanism, in addition to the commonly occurring lasR mutations, of down-regulating quorum sensing during chronic infection this may provide a selection pressure for the mucoid switch in the CF lung.

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Biosignificance of bacterial cyanogenesis in the CF lung

Cited by 34 publications

References 71 publications

Vitamin B₁₂ Status in Children With Cystic Fibrosis and Pancreatic Insufficiency

Vitamin B₁₂ Status in Children With Cystic Fibrosis and Pancreatic Insufficiency

Expression of multiplecbb₃cytochromecoxidase isoforms by combinations of multiple isosubunits inPseudomonas aeruginosa

The Mucoid Switch in Pseudomonas aeruginosa Represses Quorum Sensing Systems and Leads to Complex Changes to Stationary Phase Virulence Factor Regulation

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Biosignificance of bacterial cyanogenesis in the CF lung

Cited by 34 publications

References 71 publications

Vitamin B12 Status in Children With Cystic Fibrosis and Pancreatic Insufficiency

Vitamin B12 Status in Children With Cystic Fibrosis and Pancreatic Insufficiency

Expression of multiplecbb3cytochromecoxidase isoforms by combinations of multiple isosubunits inPseudomonas aeruginosa

The Mucoid Switch in Pseudomonas aeruginosa Represses Quorum Sensing Systems and Leads to Complex Changes to Stationary Phase Virulence Factor Regulation

Contact Info

Product

Resources

About

Vitamin B₁₂ Status in Children With Cystic Fibrosis and Pancreatic Insufficiency

Vitamin B₁₂ Status in Children With Cystic Fibrosis and Pancreatic Insufficiency

Expression of multiplecbb₃cytochromecoxidase isoforms by combinations of multiple isosubunits inPseudomonas aeruginosa