Abstract:
Introduction: Hypoxia-inducible-factor (HIF)-1 is one of the key transcription factors in angiogenesis and therefor in the adaptation to hypoxic conditions. In the past multiple studies have demonstrated the HIF-1-activation during bacterial infection, nevertheless the molecular details of this activation remained up to know unclear. In this work the role of bacterial siderophores in the HIF-1-activation during infections with Enterobacteriaceae was analyzed.
Methods: The HIF-1-activation was proved in infections with Y. enterocolitica, S. enterica and E. aerogenes. This activation could be traced back to the production and function of their siderophores. For this, generally approved methods like Elisa, Immunoblot and PCR were used.
Results: Experiments with Y. enterocolitica, S. enterica and E. aerogenes and the application of their siderophores yersiniabactin, salmochelin and aerobactin caused a hypoxia-independent HIF-1-activation in the human host cells. In contrast to this, after iron saturation of the siderophores the HIF-1-activation was completely nullified. Also siderophore-uptake-negative bacterial mutants did not show this activation in any of the experiments.
Conclusion: Taken together this work shows an unknown role of bacterial siderophores in the hypoxia-independant activation of HIF-1 during bacterial infection.