MediTest
Submitted by mrhodes40 on Sat, 2007-05-12 19:29

Chlamydia pneumoniae directly interferes with HIF-1alpha stabilization in human host cells.

Rupp J, et al

 Institute of Medical Microbiology and Hygiene, Center for Structural and Cell Biology in Medicine, University of Luebeck, 23538 Luebeck, Germany.

Chlamydiaceae are obligate intracellular bacteria that cause endemic trachoma, sexually transmitted diseases and respiratory infections. The course of the diseases is determined by local inflammatory immune responses and the propensity of the pathogen to replicate within infected host cells. Both features require energy which is inseparably coupled to oxygen availability in the microenvironment. Hypoxia-inducible factor-1 (HIF-1) regulates crucial genes involved in the adaptation to low oxygen concentrations, cell metabolism and the innate immune response. Here we report that Chlamydia pneumoniae directly interferes with host cell HIF-1alpha regulation in a biphasic manner. In hypoxia, C. pneumoniae infection had an additive effect on HIF-1alpha stabilization resulting in enhanced glucose uptake during the early phase of infection. During the late phase of intracellular chlamydial replication, host cell adaptation to hypoxia was actively silenced by pathogen-induced HIF-1alpha degradation. HIF-1alpha was targeted by the chlamydial protease-like activity factor, which was secreted into the cytoplasm of infected cells. Direct interference with HIF-1alpha stabilization was essential for efficient C. pneumoniae replication in hypoxia and highlights a novel strategy of adaptive pathogen-host interaction in chlamydial diseases.

PMID: 17490410 [PubMed - as supplied by publisher

This cool paper Jim found shows how clever the Cpn really is, it is changing the cell's genes as it lives there so that it can have a favorable environment. Essentially the CPn has taken over the cell's energy and oxygen for its own use, this causes a low oxygen environment. No problem, CPn just changes the cell's genes so the cell can adjust to a low O2 environment by upregulating the HIF-1a. Later in the replication cycle the HIF1a was broken down by injecting protease directly into the cytoplasm of the cell. The upshot is the CPn directly interferes with this adaptive response for its own benefit. Is it any wonder we do not feel well?

no link out, The whole paper is expensive, but I included the whole abstract here.  marie