title: Hypoxia Reduces the Pathogenicity of Pseudomonas aeruginosa by Decreasing the Expression of Multiple Virulence Factors.
abstract: Our understanding of how the course of opportunistic bacterial infection is influenced by the microenvironment is limited. We demonstrate that the pathogenicity of Pseudomonas aeruginosa strains derived from acute clinical infections is higher than that of strains derived from chronic infections, where tissues are hypoxic. Exposure to hypoxia attenuated the pathogenicity of strains from acute (but not chronic) infections, implicating a role for hypoxia in regulating bacterial virulence. Mass spectrometric analysis of the secretome of P. aeruginosa derived from an acute infection revealed hypoxia-induced repression of multiple virulence factors independent of altered bacterial growth. Pseudomonas aeruginosa lacking the Pseudomonas prolyl-hydroxylase domain-containing protein, which has been implicated in bacterial oxygen sensing, displays reduced virulence factor expression. Furthermore, pharmacological hydroxylase inhibition reduces virulence factor expression and pathogenicity in a murine model of pneumonia. We hypothesize that hypoxia reduces P. aeruginosa virulence at least in part through the regulation of bacterial hydroxylases.
authors.affiliation: Conway Institute and.
authors.forename: Bettina
authors.initials: B
authors.lastname: Schaible
authors.affiliation: Systems Biology Ireland, University College Dublin.
authors.forename: Javier
authors.initials: J
authors.lastname: Rodriguez
authors.affiliation: Systems Biology Ireland, University College Dublin.
authors.forename: Amaya
authors.initials: A
authors.lastname: Garcia
authors.affiliation: Edinburgh Cancer Research Centre, University of Edinburgh, United Kingdom.
authors.forename: Alexander
authors.initials: A
authors.lastname: von Kriegsheim
authors.affiliation: Centre for Microbial Host Interactions, Department of Science, Institute of Technology Tallaght-Dublin, and.
authors.forename: Siobhán
authors.initials: S
authors.lastname: McClean
authors.affiliation: Conway Institute and.
authors.forename: Caitríona
authors.initials: C
authors.lastname: Hickey
authors.affiliation: Conway Institute and.
authors.forename: Ciara E
authors.initials: CE
authors.lastname: Keogh
authors.affiliation: Conway Institute and.
authors.forename: Eric
authors.initials: E
authors.lastname: Brown
authors.affiliation: Department of Clinical Microbiology, St Vincent's University Hospital, Dublin, Ireland; and.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Schaffer
authors.affiliation: Université de Nantes, IRS2 Nantes Biotech, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Broquet
authors.affiliation: Conway Institute and.|Systems Biology Ireland, University College Dublin.
authors.forename: Cormac T
authors.initials: CT
authors.lastname: Taylor
mesh_terms: D036002:ADP Ribose Transferases / Q000378:metabolism; D000208:Acute Disease; D000818:Animals; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D001427:Bacterial Toxins / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology*; D060833:Cellular Microenvironment / Q000502:physiology; D002908:Chronic Disease; D005098:Exotoxins / Q000378:metabolism; D051379:Mice; D010100:Oxygen / Q000494:pharmacology; D064828:Prolyl Hydroxylases / Q000378:metabolism; D064800:Prolyl-Hydroxylase Inhibitors / Q000378:metabolism; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity*; D017262:Siderophores / Q000378:metabolism; D037521:Virulence Factors / Q000032:analysis / Q000378:metabolism*; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D005098:Exotoxins; D010100:Oxygen; D064828:Prolyl Hydroxylases; D064800:Prolyl-Hydroxylase Inhibitors; D017262:Siderophores; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
keywords: Alkaline protease; Exotoxin A; Hydroxylase.; Infection; Oxygen; Virulence