Hypoxia reduces the pathogenicity of Pseudomonas aeruginosa by decreasing the expression of multiple virulence factors

Bettina Schaible, Javier Rodriguez, Amaya Garcia, Alexander von Kriegsheim, Siobhán McClean, Caitríona Hickey, Ciara E Keogh, Eric Brown, Kirsten Schaffer, Alexis Broquet, Cormac T Taylor

Research output: Contribution to journalArticlepeer-review

Abstract

Our understanding of how the course of opportunistic bacterial infection is influenced by the microenvironment is limited. We demonstrate that the pathogenicity of P. 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. P. aeruginosa lacking the pseudomonas prolyl-hydroxylase domain containing protein (PPHD), 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 hypoxia reduces P. aeruginosa virulence at least in part through the regulation of bacterial hydroxylases.

Original languageEnglish
JournalThe Journal of Infectious Diseases
Early online date25 Mar 2017
DOIs
Publication statusE-pub ahead of print - 25 Mar 2017
Externally publishedYes

Keywords

  • Alkaline protease
  • Exotoxin
  • Hydroxylase
  • Infection
  • Oxygen
  • Virulence Factors, Bordetella

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