Format

Send to

Choose Destination
PLoS One. 2010 Jul 14;5(7):e11576. doi: 10.1371/journal.pone.0011576.

Activation of hypoxia inducible factor 1 is a general phenomenon in infections with human pathogens.

Author information

1
Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum Tübingen, Eberhard-Karls-Universität, Tübingen, Germany.

Abstract

BACKGROUND:

Hypoxia inducible factor (HIF)-1 is the key transcriptional factor involved in the adaptation process of cells and organisms to hypoxia. Recent findings suggest that HIF-1 plays also a crucial role in inflammatory and infectious diseases.

METHODOLOGY/PRINCIPAL FINDINGS:

Using patient skin biopsies, cell culture and murine infection models, HIF-1 activation was determined by immunohistochemistry, immunoblotting and reporter gene assays and was linked to cellular oxygen consumption. The course of a S. aureus peritonitis was determined upon pharmacological HIF-1 inhibition. Activation of HIF-1 was detectable (i) in all ex vivo in biopsies of patients suffering from skin infections, (ii) in vitro using cell culture infection models and (iii) in vivo using murine intravenous and peritoneal S. aureus infection models. HIF-1 activation by human pathogens was induced by oxygen-dependent mechanisms. Small colony variants (SCVs) of S. aureus known to cause chronic infections did not result in cellular hypoxia nor in HIF-1 activation. Pharmaceutical inhibition of HIF-1 activation resulted in increased survival rates of mice suffering from a S. aureus peritonitis.

CONCLUSIONS/SIGNIFICANCE:

Activation of HIF-1 is a general phenomenon in infections with human pathogenic bacteria, viruses, fungi and protozoa. HIF-1-regulated pathways might be an attractive target to modulate the course of life-threatening infections.

PMID:
20644645
PMCID:
PMC2904385
DOI:
10.1371/journal.pone.0011576
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center