Hypoxia Reduces the Pathogenicity of Pseudomonas aeruginosa by Decreasing the Expression of Multiple Virulence Factors. (25th March 2017)

• Record Type: Journal Article
• Authors: Schaible, Bettina; Rodriguez, Javier; Garcia, Amaya; von Kriegsheim, Alexander; McClean, Siobhán; Hickey, Caitríona; Keogh, Ciara E.; Brown, Eric; Schaffer, Kirsten; Broquet, Alexis; Taylor, Cormac T.
• Is Part Of: Journal of infectious diseases. Volume 215:Number 9(2017:May 01)
• Page Start: 1459
• Page End: 1467
• Publication Date: 2017-03-25
• Subjects: Infection -- Virulence -- Exotoxin A -- Alkaline protease -- Oxygen -- Hydroxylase.; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jix139
• Languages: English
• ISSNs: 0022-1899

Abstract

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.