title: Oxygen, cyanide and energy generation in the cystic fibrosis pathogen Pseudomonas aeruginosa.
abstract: Pseudomonas aeruginosa is a gram-negative, rod-shaped bacterium that belongs to the gamma-proteobacteria. This clinically challenging, opportunistic pathogen occupies a wide range of niches from an almost ubiquitous environmental presence to causing infections in a wide range of animals and plants. P. aeruginosa is the single most important pathogen of the cystic fibrosis (CF) lung. It causes serious chronic infections following its colonisation of the dehydrated mucus of the CF lung, leading to it being the most important cause of morbidity and mortality in CF sufferers. The recent finding that steep O2 gradients exist across the mucus of the CF-lung indicates that P. aeruginosa will have to show metabolic adaptability to modify its energy metabolism as it moves from a high O2 to low O2 and on to anaerobic environments within the CF lung. Therefore, the starting point of this review is that an understanding of the diverse modes of energy metabolism available to P. aeruginosa and their regulation is important to understanding both its fundamental physiology and the factors significant in its pathogenicity. The main aim of this review is to appraise the current state of knowledge of the energy generating pathways of P. aeruginosa. We first look at the organisation of the aerobic respiratory chains of P. aeruginosa, focusing on the multiple primary dehydrogenases and terminal oxidases that make up the highly branched pathways. Next, we will discuss the denitrification pathways used during anaerobic respiration as well as considering the ability of P. aeruginosa to carry out aerobic denitrification. Attention is then directed to the limited fermentative capacity of P. aeruginosa with discussion of the arginine deiminase pathway and the role of pyruvate fermentation. In the final part of the review, we consider other aspects of the biology of P. aeruginosa that are linked to energy metabolism or affected by oxygen availability. These include cyanide synthesis, which is oxygen-regulated and can affect the operation of aerobic respiratory pathways, and alginate production leading to a mucoid phenotype, which is regulated by oxygen and energy availability, as well as having a role in the protection of P. aeruginosa against reactive oxygen species. Finally, we consider a possible link between cyanide synthesis and the mucoid switch that operates in P. aeruginosa during chronic CF lung infection.
authors.affiliation: Division of Biology, Faculty of Natural Sciences, Imperial College London, Sir Alexander Fleming Building, London SW7 2AZ, UK.
authors.forename: Huw D
authors.initials: HD
authors.lastname: Williams
authors.forename: James E A
authors.initials: JE
authors.lastname: Zlosnik
authors.forename: Ben
authors.initials: B
authors.lastname: Ryall
mesh_terms: D003550:Cystic Fibrosis / Q000378:metabolism / Q000382:microbiology*; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D006856:Hydrogen Cyanide / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000378:metabolism / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D020545:Respiratory Mucosa / Q000378:metabolism / Q000382:microbiology
chemical_list: D006856:Hydrogen Cyanide; D010100:Oxygen