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

Comments

I had to be this clever to survive so well and to be responsible for so much human misery without being found out I suppose.   Any idea when it was published?Michele: Wheldon CAP1st May 2006 IBS, sinusitis, alopecia, asthma, peripheral neuropathy. 26th March 2007 continuous Flagyl at 400mg with 5 day pulses at 1200mg every three weeks. Spokesperson for Ella, RRMS Cap Started 16 March 2006

Michèle (UK) GFA: Wheldon CAP 1st May 2006. Daily Doxy, Azi MWF, metro pulse.

Completely current, Michèle: the abstract was May 8th 2007, ahead of publication........Sarah An Itinerary in Light and Shadow  

Completed Stratton/Wheldon regime for aggressive secondary progressive MS in June 2007, after four years, three of which intermittent.   Still improving bit by bit and no relapses since finishing treatment.

For years I have been much worse at high altitudes. Now I know why. Thank you for this great info.

Combined Antibiotic Protocol for chlamydia pneumoniae in fibromyalgia, interstitial cystitis, sinus: minocycline, Zithromycin, Flagyl

minocycline, azithromycine, metronidazole 2007-2009, chelation for lead poisoning, muscle pain, insomnia, interstitial cystitis (almost well), sinus, dry eyes, stiff neck, veins, hypothyroid, TMJ, hip joints (no longer hurt)

I attempted to vote for this node, but only got a "user warning."

Combined Antibiotic Protocol for chlamydia pneumoniae in fibromyalgia, interstitial cystitis, sinus: minocycline, Zithromycin, Flagyl

minocycline, azithromycine, metronidazole 2007-2009, chelation for lead poisoning, muscle pain, insomnia, interstitial cystitis (almost well), sinus, dry eyes, stiff neck, veins, hypothyroid, TMJ, hip joints (no longer hurt)

Yep, looks like the vote system is not functioning. We'll look into it. CAP for Chlamydia pneumonia since 11/04. 25yrs CFS & FMS- Currently: 150mg INH, 200 Doxycycline, 500mg MWF Azithromycin, 500mg Tini daily (Continuous protocol)

This might also account for those times when I just lie there and pant for breath. I think it was Jim K who called it an inability to breathe fluidly, which describes it very well.The episodes are becoming less frequent, and I am learning to recover more quickly (get under the electric blanket, set to "stun" or higher.) RonOn CAP for CFS starting 01/06 (NE Ohio, USA) Currently: doxy & zith -- continous; metronidazole -- 5 days on, 7 days off.Get the research results you paid for: support

RonOn CAP for CFS starting 01/06 (NE Ohio, USA)Began rifampin trial 1/14/09Currently: on intermittent

This explains a lot. The hypoxia inside cells would greatly encourage henchmen microbes. High oxygen levels encourage good bacteria. Hypoxia favor pathogens. Breathing 100% oxygen at ordinary air pressure won't get the oxygen into the cells. Those little oxygen testers placed on a fingertip may say that the blood is well oxygenated, but the patient still be hypoxic. My theory is that without sufficient oxygen, the cell energy machinery can't run, and so hemoglobin synthesis breaks down. Perhaps this is why we get porphyria. During weeks of daily hyperbaric oxygen treatments I had no reaction to full doses of all the antibioitics. I think the sufficient level of oxygen inside the cells prevented porphyria and mopped up the endotoxins. Insurance currently won't pay for us to get hyperbaric oxygen. Sick, disabled people can't come up with the cash to pay for enough to get them well. Maybe this research into HIF-1alpha could change this. Or if we just had a pill that would stop the enzyme damage.

Combined Antibiotic Protocol for chlamydia pneumoniae in fibromyalgia, interstitial cystitis, sinus: minocycline, Zithromycin, Flagyl

minocycline, azithromycine, metronidazole 2007-2009, chelation for lead poisoning, muscle pain, insomnia, interstitial cystitis (almost well), sinus, dry eyes, stiff neck, veins, hypothyroid, TMJ, hip joints (no longer hurt)

Janice, this is fascinating.
"During weeks of daily hyperbaric oxygen treatments I had no reaction to full doses of all the antibioitics. I think the sufficient level of oxygen inside the cells prevented porphyria and mopped up the endotoxins"
In the early days of becoming ill, I sought out a doctor who runs a hyberbaric center. I had one treatment but felt like it exacerbated my symptoms.I am intrigued by the possibility that it would mitigate die off symptoms while taking the CAP.
I also had to pay out of pocket for the treatment. That was one reason I didn't continue. Too bad insurance won't cover this.
How did you manage to get daily treatments?

Raven
CAP since 8-05 for Cpn and Mycoplasma P. for MS and/or CFS

Feeling 98% well-going for 100. Very low test for Cpn. CAP since 8-05 for Cpn/Mycoplasma P.,Lyme, Bartonella, Mold exposure,NAC,BHRT, MethyB12 FIR Sauna. 1-18-11 begin new treatment plan with naturopath

 As I understand it, porphyria is caused by inadequate ATP, not inadequate O2. Perhaps someone who knows  little more cell biology than I might help us understand the relationship, if any, between intracellular hypoxia and heme production. Eric, you around? CAP for Chlamydia pneumonia since 11/04. 25yrs CFS & FMS- Currently: 150mg INH, 200 Doxycycline, 500mg MWF Azithromycin, 500mg Tini daily (Continuous protocol)

If I understand the Krebs cycle, one molecule of glucose is turned into pyruvate, yielding 2 ATP. In the presence of oxygen, the mitochondria then use aerobic respiration to produce 34 molecules of ATP. Without oxygen the pyruvate is fermented to lactic acid, yielding only 2 ATP. Also, I have read that hypoxia and cancer are linked. Combined Antibiotic Protocol for chlamydia pneumoniae in fibromyalgia, interstitial cystitis, sinus: minocycline, Zithromycin, Flagyl

minocycline, azithromycine, metronidazole 2007-2009, chelation for lead poisoning, muscle pain, insomnia, interstitial cystitis (almost well), sinus, dry eyes, stiff neck, veins, hypothyroid, TMJ, hip joints (no longer hurt)

Interesting, Janice.Perhaps this is the cause of muscle burning I sometimes experience (especially the gluts). Lactic acid can cause burning sensations in the muscles.
Raven

Feeling 98% well-going for 100. Very low test for Cpn. CAP since 8-05 for Cpn/Mycoplasma P.,Lyme, Bartonella, Mold exposure,NAC,BHRT, MethyB12 FIR Sauna. 1-18-11 begin new treatment plan with naturopath

The HIF-1 alpha research may show the mechanism for what happens in CFS. This seems to tie together much of what I have read over the years. Mitochondrial failure has been blamed for causing CFS. ADP doesn't get recycled back to ATP fast enough. If someone with CFS thinks they are having a good day, and push too far, ADP may be further broken down to AMP. This causes post exertion fatigue. The body has to start from scratch making ATP. Some of the supplements our good doctors have us taking help this energy cycle. D-ribose. Co enzyme Q. B3 or niacin. Magnesium.This makes me angrier at cpn. No wonder we feel horrible. Combined Antibiotic Protocol for chlamydia pneumoniae in fibromyalgia, interstitial cystitis, sinus: minocycline, Zithromycin, Flagyl

minocycline, azithromycine, metronidazole 2007-2009, chelation for lead poisoning, muscle pain, insomnia, interstitial cystitis (almost well), sinus, dry eyes, stiff neck, veins, hypothyroid, TMJ, hip joints (no longer hurt)

Janice, you said, "Also, I have read that hypoxia and cancer are linked." That also might explain why people with CFS die much younger from cancer if they get it (almost 10 years.)  They get cancer at about the same rate as non-CFS, but die younger.RonOn CAP for CFS starting 01/06 (NE Ohio, USA) Currently: doxy & zith -- continous; metronidazole -- 5 days on, 7 days off.

RonOn CAP for CFS starting 01/06 (NE Ohio, USA)Began rifampin trial 1/14/09Currently: on intermittent

JaniceYou saidIf someone with CFS thinks they are having a good day, and push too far, ADP may be further broken down to AMP. This causes post exertion fatigue. The body has to start from scratch making ATP. That makes the most sense so far