Oxygen, Cyanide and Energy Generation in the Cystic Fibrosis Pathogen Pseudomonas aeruginosa

Williams, Huw D.; Zlosnik, James E. A.; Ryall, Ben

doi:10.1016/s0065-2911(06)52001-6

Cited by 157 publications

(196 citation statements)

References 321 publications

Supporting

Mentioning

190

Contrasting

Order By: Relevance

“…Azurin, like cytochrome c, mediates the transfer of electrons from the cytochrome bc 1 complex to various terminal reductases (41). It is known that cytochrome c 551 NirM, the electron donor to nitrite reductase NirS, forms a tight complex with azurin (59).…”

Section: Resultsmentioning

confidence: 99%

Protein Network of the Pseudomonas aeruginosa Denitrification Apparatus

et al. 2016

View full text Add to dashboard Cite

Oxidative phosphorylation using multiple-component, membrane-associated protein complexes is the most effective way for a cell to generate energy. Here, we systematically investigated the multiple protein-protein interactions of the denitrification apparatus of the pathogenic bacterium Pseudomonas aeruginosa. During denitrification, nitrate (Nar), nitrite (Nir), nitric oxide (Nor), and nitrous oxide (Nos) reductases catalyze the reaction cascade of NO 3؊ ¡ NO 2؊ ¡ NO ¡ N 2 O ¡ N 2 . Genetic experiments suggested that the nitric oxide reductase NorBC and the regulatory protein NosR are the nucleus of the denitrification protein network. We utilized membrane interactomics in combination with electron microscopy colocalization studies to elucidate the corresponding protein-protein interactions. The integral membrane proteins NorC, NorB, and NosR form the core assembly platform that binds the nitrate reductase NarGHI and the periplasmic nitrite reductase NirS via its maturation factor NirF. The periplasmic nitrous oxide reductase NosZ is linked via NosR. The nitrate transporter NarK2, the nitrate regulatory system NarXL, various nitrite reductase maturation proteins, NirEJMNQ, and the Nos assembly lipoproteins NosFL were also found to be attached. A number of proteins associated with energy generation, including electron-donating dehydrogenases, the complete ATP synthase, almost all enzymes of the tricarboxylic acid (TCA) cycle, and the Sec system of protein transport, among many other proteins, were found to interact with the denitrification proteins. This deduced nitrate respirasome is presumably only one part of an extensive cytoplasmic membrane-anchored protein network connecting cytoplasmic, inner membrane, and periplasmic proteins to mediate key activities occurring at the barrier/interface between the cytoplasm and the external environment. IMPORTANCEThe processes of cellular energy generation are catalyzed by large multiprotein enzyme complexes. The molecular basis for the interaction of these complexes is poorly understood. We employed membrane interactomics and electron microscopy to determine the protein-protein interactions involved. The well-investigated enzyme complexes of denitrification of the pathogenic bacterium Pseudomonas aeruginosa served as a model. Denitrification is one essential step of the universal N cycle and provides the bacterium with an effective alternative to oxygen respiration. This process allows the bacterium to form biofilms, which create low-oxygen habitats and which are a key in the infection mechanism. Our results provide new insights into the molecular basis of respiration, as well as opening a new window into the infection strategies of this pathogen.

show abstract

Section: Resultsmentioning

confidence: 99%

Protein Network of the Pseudomonas aeruginosa Denitrification Apparatus

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Traditionally, the organisms other than P. aeruginosa known to be cyanogenic are: Pseudomonas fluorescens, Pseudomonas aureofaciens, Pseudomonas chlororaphis, Chromobacterium violaceum and Rhizobium leguminosarum [16,39]. These organisms are not usually isolated from patients with CF.…”

Section: Respiratory Infections Fj Gilchrist Et Almentioning

confidence: 99%

Variation in hydrogen cyanide production between different strains of Pseudomonas aeruginosa

Gilchrist¹,

Alcock²,

Belcher³

et al. 2011

European Respiratory Journal

View full text Add to dashboard Cite

There is increasing interest in using the cyanogenic properties of Pseudomonas aeruginosa to develop a nonmicrobiological method for its detection. Prior to this, the variation in cyanide production between different P. aeruginosa strains needs to be investigated.Hydrogen cyanide (HCN) released into the gas phase by 96 genotyped P. aeruginosa samples was measured using selected ion flow tube-mass spectrometry after 24, 48, 72 and 96 h of incubation. The HCN produced by a range of non-P. aeruginosa cultures and incubated blank plates was also measured.All P. aeruginosa strains produced more HCN than the control samples, which generated extremely low levels. Analysis across all time-points demonstrated that nonmucoid samples produced more HCN than the mucoid samples (p50.003), but this relationship varied according to strain. There were clear differences in the headspace HCN concentration for different strains. Multivariate analysis of headspace HCN for the commonest strains (Liverpool, Midlands_1 and Stoke-on-Trent, UK) revealed a significant effect of strain (p,0.001) and a borderline interaction of strain and phenotype (p50.051).This evidence confirms that all P. aeruginosa strains produce HCN but to varying degrees and generates interest in the possible future clinical applications of the cyanogenic properties of P. aeruginosa.

show abstract

“…An interesting aspect of the physiology of P. aeruginosa is that it is one of a limited number of bacteria that can synthesise hydrogen cyanide [7]. In culture, the levels of cyanide can reach 300-500 mM [7][8][9]. The purpose of cyanide production by P. aeruginosa is unclear but it has been shown to be the mediating factor in the paralytic killing model of Caenorhabditis elegans by P. aeruginosa, raising the possibility that it may be significant in pathogenicity [10].…”

mentioning

confidence: 99%

“…Cyanide can inhibit many cellular processes, but its most well-recognised effect is to inhibit aerobic respiration through its interaction with the terminal oxidases of aerobic respiratory chains. P. aeruginosa may avoid the toxic effects of cyanide as it can synthesise a respiratory chain terminated by a cyanide insensitive terminal oxidase [8,12,13], although active detoxification mechanisms are also likely to play an important role [14,15]. Cyanide production by P. aeruginosa occurs at low oxygen concentrations; conditions which P. aeruginosa are believed to inhabit in the mucus layer of the CF lung [16].…”

mentioning

confidence: 99%

Pseudomonas aeruginosa, cyanide accumulation and lung function in CF and non-CF bronchiectasis patients

Ryall¹,

Davies²,

Wilson³

et al. 2008

European Respiratory Journal

100

View full text Add to dashboard Cite

In patients with cystic fibrosis (CF) and non-CF bronchiectasis, Pseudomonas aeruginosa is the most important respiratory pathogen. It is able to synthesise hydrogen cyanide, a potent inhibitor of cellular respiration.The present study investigated whether cyanide is present in the sputum of CF and non-CF bronchiectasis patients infected with P. aeruginosa, and whether the detection of cyanide affected lung function. Cyanide was measured in sputum using a cyanide ion selective electrode.Cyanide was detected in sputum from 15 out of 25 CF and non-CF bronchiectasis patients with current P. aeruginosa infection; however, it was not detected in any of the 10 patients without this organism. Maximum levels were 130 mM (mean¡SE 72¡6.6 mM). Concurrent lung function data were available on all 21 P. aeruginosa-infected CF patients; the group with measurable sputum cyanide (n511) was not different from those without (n510) on the basis of age or sex. However, those with detectable cyanide had significantly poorer lung function than those without (forced expiratory volume in one second (% predicted) 26.8¡3.8 versus 46.0¡6.7%; forced vital capacity (% pred) 44.4¡4.9 versus 60.1¡7.7%).Cyanide is detectable in sputum from cystic fibrosis and non-cystic fibrosis bronchiectasis patients infected with Pseudomonas aeruginosa, and is also associated with impaired lung function.

show abstract

Oxygen, Cyanide and Energy Generation in the Cystic Fibrosis Pathogen Pseudomonas aeruginosa

Cited by 157 publications

References 321 publications

Protein Network of the Pseudomonas aeruginosa Denitrification Apparatus

Protein Network of the Pseudomonas aeruginosa Denitrification Apparatus

Variation in hydrogen cyanide production between different strains of Pseudomonas aeruginosa

Pseudomonas aeruginosa, cyanide accumulation and lung function in CF and non-CF bronchiectasis patients

Contact Info

Product

Resources

About