TY  - JOUR
A1  - Werth, Nadine
A1  - Beerlage, Christiane
A1  - Rosenberger, Christian
A1  - Yazdi, Amir Sadegh
A1  - Edelmann, Markus
A1  - Amr, Amro
A1  - Bernhardt, Wanja
A1  - Eiff, Christof von
A1  - Becker, Karsten
A1  - Schäfer, Andrea
A1  - Peschel, Andreas
A1  - Kempf, Volkhard A. J.
T1  - Activation of hypoxia inducible factor 1 is a general phenomenon in infections with human pathogens
T2  - PLoS One
N2  - 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.
Y1  - 2010
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/22566
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-114214
SN  - 1932-6203
N1  - Copyright: © 2010 Werth et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 5
IS  - (7): e11576
ER  -