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Hypoxia modulates infection of epithelial cells by Pseudomonas aeruginosa

Bettina Schaible1, Siobhán McClean, Andrew Selfridge

  • 1UCD School of Medicine and Medical Science and The Conway Institute, University College Dublin, Dublin, Ireland.

Plos One
|February 19, 2013
PubMed

Insights

Hypoxia reduces Pseudomonas aeruginosa (P. aeruginosa) entry into host cells, decreasing infection severity and mortality. Pharmacological targeting of host pathways offers potential new therapies for P. aeruginosa infections.

Area of Science:

  • Microbiology
  • Host-Pathogen Interactions
  • Cellular Physiology

Background:

  • Pseudomonas aeruginosa is an opportunistic pathogen causing lung and wound infections.
  • Hypoxia, common in infected tissues, influences host immunity and bacterial virulence.
  • The impact of hypoxia on host-pathogen interactions like bacterial adhesion is not well understood.

Purpose of the Study:

  • To investigate the effect of hypoxia on P. aeruginosa internalization into host epithelial cells.
  • To explore the role of hypoxia-inducible factor (HIF) and Rho kinase pathways in this interaction.
  • To evaluate the therapeutic potential of targeting these pathways in P. aeruginosa infections.

Main Methods:

  • In vitro studies using cultured epithelial cells and P. aeruginosa.
  • Pharmacological inhibition of hydroxylases (DMOG) and Rho kinase.
  • Genetic manipulation of HIF-2α expression.
  • In vivo pneumonia infection model in mice.

Main Results:

  • Hypoxia significantly decreased P. aeruginosa internalization into epithelial cells, reducing host cell death.
  • The hydroxylase inhibitor DMOG mimicked hypoxia's effect.
  • Reduced HIF-2α expression or Rho kinase activity diminished hypoxia's impact.
  • DMOG treatment before infection in vivo markedly reduced mortality.

Conclusions:

  • Hypoxia impairs P. aeruginosa internalization into epithelial cells.
  • Pharmacological modulation of host HIF and Rho kinase pathways shows therapeutic promise.
  • Targeting host pathways involved in hypoxia response could be a novel strategy for treating P. aeruginosa infections.

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