Senior Member

I thought this was interesting. Changing a single atom on a B1 molecule is enough to disrupt an e-coli bacterium, by preventing glutamate molecules from acting as a catalyst. This is more along the lines of what I see as the core dysfunction of ME: one molecule in one of the pathways in a cell not doing its job properly (maybe in a small but critical part of the brain). Maybe a critical molecule is misfolding, in a prion-like way. Maybe another molecule is there in the wrong ratio, interfering with the critical molecule. This is the sort of dysfunction that can switch state quickly in response to another chemical, giving the rapid temporary remissions that have been observed.


Senior Member
Methylfolate Trap Promotes Bacterial Thymineless Death by Sulfa Drugs.
The methylfolate trap, a metabolic blockage associated with anemia, neural tube defects, Alzheimer's dementia, cardiovascular diseases, and cancer, was discovered in the 1960s, linking the metabolism of folate, vitamin B12, methionine and homocysteine. However, the existence or physiological significance of this phenomenon has been unknown in bacteria, which synthesize folate de novo. Here we identify the methylfolate trap as a novel determinant of the bacterial intrinsic death by sulfonamides, antibiotics that block de novo folate synthesis. Genetic mutagenesis, chemical complementation, and metabolomic profiling revealed trap-mediated metabolic imbalances, which induced thymineless death, a phenomenon in which rapidly growing cells succumb to thymine starvation. Restriction of B12 bioavailability, required for preventing trap formation, using an "antivitamin B12" molecule, sensitized intracellular bacteria to sulfonamides. Since boosting the bactericidal activity of sulfonamides through methylfolate trap induction can be achieved in Gram-negative bacteria and mycobacteria, it represents a novel strategy to render these pathogens more susceptible to existing sulfonamides.
"antibiotics that block de novo folate synthesis" - Bactrim comes to mind.