New ‘Subway Map’ of Lyme Disease Pathways Identifies Potential New Treatment Targets

thanks for the link Rainy
good that they are looking at novel ways of making targeted drugs

i would like to see more of this type of approach - as currently there is only a tiny amount of research in this direction

i only skimmed the article - and they state that these are just starting points for further research - but they do seem to have a large gap to close.
my read on it is the drugs they came up with are currently approx 1000x less strong than doxycycline based on comparing MIC ( low micrograms / ml for doxy vs low milligrams / ml for the enzyme blockers they came up with)

still its another angle - and good to see people are actually working on new ways to find a better antibiotic

it looks like Tufts has raised some money - or obtained government grant money to do this type of research as all authors are listed as from the same University in Boston USA - so perhaps we will see more from this group in the future

"Graduate School of Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts, USA
Tufts Lyme Disease Initiative, Tufts University, Boston, Massachusetts, USA"

The summary of this research is that borrelia has a very reduced genome, and in several cases relies on a single gene for an essential function. In such cases, blocking the function of that one protein leads to the death of the spirochete.

Specific targets that these researchers identified include folate metabolism (serine hydroxymethyltransferase), vitamin B6 metabolism (pyridoxal kinase), glycolysis (several enzymes), cell wall synthesis (alanine racemase), and reliance on a small number of enzymes for nucleotide synthesis.

The specific drugs that they tested were cycloserine (inhibitor of alanine racemase), bromopyruvate (glycolysis inhibitor), theophylline (asthma drug, inhibits pyridoxal kinase), and pemetrexed (anti-folate cancer drug, inhibits serine hydroxymethyltransferase). None of these are considered viable treatment options, but this research is a good overview of what types of drugs might be useful for killing borrelia.

Some of these potential vulnerabilities of borrelia were already known, Borrelia's limited folate metabolism is known to be susceptible to dapsone, and the limited number of nucleoside kinase enzymes may in part explain borrelia's unusual susceptibility to nucleoside analogues. The exclusive reliance on glycolysis for ATP production has also been suggested as a therapeutic target: https://pubmed.ncbi.nlm.nih.gov/37513809/