The tolerance and treatment of Lyme disease, which is caused by the Borrelia burgdorferi bacterium and is transmitted through infected tick bites, has always been hard to combat. The standard therapy for Lyme Disease remains antibiotics such as doxycycline, however, even after being administered, these antibiotics are not fully wiping out the infection which leads to the phenomenon called Post Treatment Lyme Disease Syndrome (PTLDS).
After all, a solution might be at hand as Virginia Commonwealth University VCU researchers have just recently pinpointed an outstanding therapeutic target that can single handedly change the game for Lyme disease treatment which is an enzyme known as lactate dehydrogenase (BbLDH).
Burgdorferi BbLDH (Borrelia burgdorferi lactate dehydrogenase): Whatโs Its Role in Lyme Disease
B. burgdorferi is like no other bacterium in regard to its metabolic structure. It does not contain many bio-synthetic pathways fundamental for the majority of living things, for instance, the organismโs capacity to build amino acids and fatty acids. Hence, it relies almost exclusively on a metabolic process, glycolysis, whereby glucose is metabolized into pyruvate to be converted to lactate.
The conversion process is aided by lactate dehydrogenase known as BbLDH which plays the role of balancing NADH and NAD+, which are pivotal molecules in energy metabolism.
Consequently, the bacterium being dependent on BbLDH (Borrelia burgdorferi lactate dehydrogenase) for power generation, makes it extremely defenseless to any changes made to this energy production process.
In the absence of BbLDH, B. burgdorferi energy production falls below the threshold required for its survival and multiplication. This makes this organism susceptible and a possible candidate for drug intervention in the treatment of Lyme Disease.
The Discovery of BbLDH (Borrelia burgdorferi lactate dehydrogenase) Inhibitors
The VCU research team screened more than 14,000 compounds in search of BbLDH competitors, and was able to determine four that inhibited BbLDH (Borrelia burgdorferi lactate dehydrogenase) effectiveness. Two of them, methoxsalen and medicarpin, are very encouraging.
- Methoxsalen – It is being used in treatment of psoriasis and vitiligo. It acts under UV light that induces cell activity as it binds to DNA and inhibits cell activity. It was shown that methoxsalen binds to BbLDH, them being able to change the redox equilibrium.
- Medicarpin – A natural is flavonoid that has antimicrobial and anti-inflammatory effects. Medicarpin has been shown to inhibit BbLDH (Borrelia burgdorferi lactate dehydrogenase)without sustaining damage to human cells while stunting the growth of the bacteria.
Both compounds were shown to greatly diminish B. burgdorferi in vitro viability. Therefore, it can be postulated that the inhibition of BbLDH (Borrelia burgdorferi lactate dehydrogenase)makes the bacterium less able to survive and multiply, which is beneficial in formulating treatment of Lyme Disease.
Why This Discovery Matters
Lyme Disease currently has no reliable treatment aside from antibiotics which are useful in most cases but not in all. Raising issues with treatment is antibiotic resistance infection after treatment.
- There is hope that long-term use of antibiotics can be reduced with the introduction of BbLDH (Borrelia burgdorferi lactate dehydrogenase)inhibitors.
- Halting the activity of BbLDH will likely cause less dysbiosis than antibiotic treatment.
- Development of resistance is anticipated to be slower than with antibiotics because of the overdependence of B. burgdorferi on BbLDH.
This suggests that treatment approaches targeting BbLDH (Borrelia burgdorferi lactate dehydrogenase)will be more kinder and effective in treating Lyme Disease without complications or relapses.
Challenges and Next Steps
Methoxsalen and medicarpin have been shown to have positive results in vitro (in lab settings), but testing their safety and efficacy in animal models, and eventually in human trials, will require additional work. Including but not limited to:
- Selectively targeting BbLDH but not human lactate dehydrogenase.
- Changing the route of administration to target tissues were B. burgdorferi hides like joints and the central nervous system.
- Evaluating the possibility of using other therapies alongside existing antibiotics to increase their effectiveness while decreasing the likelihood of the bacteria persisting in Lyme Disease patients.
Future Lyme Disease Treatment
The advancement of this discovery has opened new avenues of treatment for Lyme Disease as it targets the diseaseโs nature. This approach provides new insight into precision medicine: where focus is on the metabolic vulnerabilities of the pathogens instead of broader diseases that are harder to treat.
The successful clinical trials of BbLDH (Borrelia burgdorferi lactate dehydrogenase)inhibitors can offer new treatment possibilities for patients suffering from chronic Lyme Disease symptoms.
Besides contributing further to our knowledge of B. burgdorferiโs metabolism, this work encourages the development of therapies that target the survival mechanisms of the pathogen. More broadly, with further development these BbLDH (Borrelia burgdorferi lactate dehydrogenase) inhibitors could become an important tool in defeating Lyme Disease and benefit patients across the world.
