H. Pylori Attacks Energy Generation via mTORC1 Inhibition

[AdamS]

Research: https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(18)30203-8

Article: https://m.phys.org/news/2018-05-disease-causing-stomach-bug-energy-host.html

Highlights

• •Helicobacter pylori inhibit mTORC1 signaling activity by a VacA-dependent mechanism
• •Mitochondrial targeting by VacA disrupts amino acid homeostasis sensed by mTORC1
• •VacA intoxication drives mTORC1 dissociation from lysosomes into an inactive complex
• •Inhibition of mTORC1 activates autophagy through the Ulk-1 protein kinase complex

Summary
Helicobacter pylori (Hp) vacuolating cytotoxin (VacA) is a bacterial exotoxin that enters host cells and induces mitochondrial dysfunction. However, the extent to which VacA-dependent mitochondrial perturbations affect overall cellular metabolism is poorly understood. We report that VacA perturbations in mitochondria are linked to alterations in cellular amino acid homeostasis, which results in the inhibition of mammalian target of rapamycin complex 1 (mTORC1) and subsequent autophagy. mTORC1, which regulates cellular metabolism during nutrient stress, is inhibited during Hpinfection by a VacA-dependent mechanism. This VacA-dependent inhibition of mTORC1 signaling is linked to the dissociation of mTORC1 from the lysosomal surface and results in activation of cellular autophagy through the Unc 51-like kinase 1 (Ulk1) complex. VacA intoxication results in reduced cellular amino acids, and bolstering amino acid pools prevents VacA-mediated mTORC1 inhibition. Overall, these studies support a model that Hp modulate host cell metabolism through the action of VacA at mitochondria.

 

[Runner5]

I happen to not have h.pylori or have ever had h.pylori (had a blood test to see if I had ever been infected which tests for past and current antibodies and a stool test for current infection). So I guess in my case I can rule that out as a cause.

 

[RWP (Rest without Peace)]

@AdamS

Hmmm. A pathogen, outside the cell, emits a toxin that inhibits mTORC1, causing a shutdown of energy production in the mitochondria. Does that sound familiar? Adam, is that why you posted this, or did you have another idea?

BTW: I don't remember which mTOR pathway Dr. Davis has found low in ME/CFS, but I don't think it was C1. Does anyone else remember which and whether that would make a significant difference in this paradigm for an unknown pathogen doing the same with ME?

RWP

 

[AdamS]

@RWP (Rest without Peace)

Yeah I posted it because I know that quite a few people showed an interest in the mTOR pathway after Ron Davis mentioned it in one of his videos last year. I’m not really sure if it links to ME/CFS though or what to make of it, I wonder if it’s of any use to Ron? @Janet Dafoe (Rose49)

 

[RWP (Rest without Peace)]

If anyone is interested in reading more (unrelated to this article's point) about Helicobacter pylori, there are 2 PR posts I've written that can provide some information.

First, H. pylori is discussed at length in this PBS documentary about the Microbiome. https://forums.phoenixrising.me/ind...ng-fecal-transplant-5-2-18.59069/#post-976758

By the way, the history of diagnosing and treating stomach ulcers and H. pylori is an excellent "Exhibit A" to use when your disbelieving doctor gives you a hard time. A quick summary (from memory, so please watch video to confirm exact details):

1. Before the 1980's, stomach ulcers were thought to be caused by "stress." (Remember doctors always use this line
at every point in time, "We now know what causes . . ." Well, they didn't, and they still don't as much as they think
they do.)
2. Then, the bacterium H. pylori was discovered and/or linked to ulcers. "Now we know what causes ulcers."
3. So, brilliant scientists as they are, they decide to kill of the bacteria with antibiotics. "Now we know how to treat what
we know is caused by this bacteria."
4. Oops! These brilliant scientists realize that, while the antibiotics do kill the bacteria, they also start creating new
problems in their ulcer patients. "OK, so we thought we knew how to treat what we know is caused by this bacteria,
but we really didn't. But we won't make a big announcement to the public that we really don't know what we're doing
so we don't lose business."
5. These brilliant scientists NOW conclude, "Well, actually . . . this bacteria is kind of good for you, at least in small
amounts. Yes, it's a problem, but we have to combat it differently."
6. I can't remember the exact "brilliant idea" that they eventually settled on, but my point is that when a doctor or scientist says, "We know . . .", just quote this historical example back to them and maybe it will shut them up!

Second, H. pylori is a bacterium that can be carried inside a parasitic flatworm (trematode), Opisthorchus viverrini. This means that the parasite is a constant source of the bacteria and could perpetuate a state of mTOR inhibition even though some bacteria gets killed off. Read a bit more here: https://forums.phoenixrising.me/index.php?entries/pt-1-cancer-mcs-and-me.2359/

RWP