AntiVitamins against Antibiotic-Resistant Superbugs

By Harit Phowatthanasathian

 “Anti” meaning against and “biotic” meaning living things, the combination, antibiotics, translates to “against living things”, or more specifically microbes. The word antibiotics, today, encompasses any drug that combats bacteria, fungi, and parasites, and was properly utilized starting in 1928 (The History of Antibiotics, 2019). The infamous Alexander Fleming, well-known for his discovery of naturally occurring antibiotics, introduced a new era in medicine and along with it saved millions of lives thereafter.  After testing for safety and refining the methodology, Fleming saved millions of soldiers in World War II from infections with small amounts of his magical penicillin. Parallel with advances in technology and medicine, the field of antibiotics branched from just bacterial infections to fungal, and parasitic, which is believed to have greatly contributed to the increased average life expectancy from 47 years in the early 1900s to over 75 years in at the turn of the 21st century (Adedeji, 2016).

Unfortunately, the overuse of the miracle drug has come at a cost; a concerning rise in antibiotic-resistant superbugs. The small fraction of bugs that survive first-line antibiotics, pass on their ability to survive to the next generation, requiring the use of higher dosages and need for more effective antibiotics. Turning a blind eye to the decades of natural selection of bacteria and fungi has propagated generations of stronger more resilient bugs, spiraling in its cyclical nature to produce antibiotic-resistant superbugs. Estimates show that 2.8 million in the United States alone have been infected by an antibiotic-resistant infection resulting in 35,000 deaths yearly (Antibiotic resistance, 2020). In addition to the overuse on the human population, antibiotics are heavily relied on in the agriculture and farming industries, resulting in widespread exposure and perpetuating the development of superbugs. The World Health Organization (WHO) has highly prioritized this emerging problem because no individual is safe from these superbugs and in a few decades, at the rate this problem is inflating, massive pandemics could be a more common occurrence. In light of this problem, the WHO and Center for Disease Control (CDC) have increased hospital precautions and restrictions on the use of general antibiotics, aiming to slow down the development of superbugs. Policies such as improved surveillance of antibiotic-resistant infections, regulating the disposal of antibiotics, and tightening the use of antibiotics on animals, have all been promoted since superbugs have been raising concerns (How to Combat Antibiotic Resistance: 5 Priorities for 2020, 2019). 

In addition to the cautioning and policies, millions of dollars have been funneled into researching a solution and as of August 2020 antivitamins might become our answer to this problem (Myupchar, 2020). Antivitamins are exactly what they sound like, agents that work against or inhibit the biological process of vitamins. Discovered in the early 1900s, antivitamin exposure presented as cases of vitamin deficiencies but later identified antivitamins as the culprit. Currently, antivitamins K, B9, and B12 are used in medical protocols for blood clotting, suppression of cancer, and more recently microbial growth. A recent study out of the University of  Göttingen by Professor Kai Tittmann has shown the extent of antivitamin’s antimicrobial effects with three naturally occurring antivitamins, antivitamin B2, B6, and 2′-methoxy-thiamine (Rabe von Pappenheim, Aldeghi and Tittmann, 2020). The target of the latter, 2′-methoxy-thiamine, is vitamin B1 in Escherichia coli’s metabolic pathways which acts as a major cofactor. Protein crystallography of the 2′-methoxy-thiamine showed the molecule acted as a toxin because of its extra oxygen on the methyl group. This extra atom interacts with the glutamate protein to remove from its reaction, effectively inhibiting this metabolic reaction in E. coli. In the team’s words, the antivitamin stopped the “dance of protons” in the metabolic pathway to produce the shown antibacterial effects (Koumoundouros, 2020). Further analysis of antivitamins’ effects on human cells, showed no noticeable adverse effects, isolating the extent of its effect to bacteria cells (Berman, 2020).

 Even though antivitamins have been around for decades, the implication of this result is a possible alternative angle to tackle antibiotic-resistant superbugs. Antivitamins’ effects are similar to that of antibiotics but use a different mechanism, allowing it to be effective against more resistant strains. It goes without saying that, years of further research is required for this breakthrough to bloom into its full potential, however, the prospect of this concept has sparked interest in a field that will become increasingly important on the journey to find a solution to the antibiotic-resistant bugs.

References:

HealthyChildren.org. 2019. The History Of Antibiotics. [online] Available at: <https://www.healthychildren.org/English/health-issues/conditions/treatments/Pages/The-History-of-Antibiotics.aspx&gt; [Accessed 10 September 2020].

Adedeji, W., 2016. THE TREASURE CALLED ANTIBIOTICS. [online] PubMed Central (PMC). Available at: <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354621/&gt; [Accessed 10 September 2020].

Who.int. 2020. Antibiotic Resistance. [online] Available at: <https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance#:~:text=A%20growing%20number%20of%20infections,medical%20costs%20and%20increased%20mortality&gt; [Accessed 10 September 2020].

Pewtrusts.org. 2019. How To Combat Antibiotic Resistance: 5 Priorities For 2020. [online] Available at: <https://www.pewtrusts.org/en/research-and-analysis/articles/2019/11/13/how-to-combat-antibiotic-resistance-5-priorities-for-2020&gt; [Accessed 10 September 2020].

Myupchar, 2020. What Are Antivitamins And How Can They Help In Treatment Of Antibiotic-Resistant Bacterial Infections – Health News , Firstpost. [online] Firstpost. Available at: <https://www.firstpost.com/health/what-are-antivitamins-and-how-can-they-help-in-treatment-of-antibiotic-resistant-bacterial-infections-8751461.html#:~:text=Now%2C%20a%20group%20of%20researchers,reviewed%20journal%20Nature%20Chemical%20Biology.&gt; [Accessed 10 September 2020].

Rabe von Pappenheim, F., Aldeghi, M. and Tittmann, K., 2020. Are Antivitamins The New Antibiotics? Researchers Develops Drug Approach Against Bacterial Infections. [online] ScienceDaily. Available at: <https://www.sciencedaily.com/releases/2020/08/200824131805.htm&gt; [Accessed 10 September 2020].

Koumoundouros, T., 2020. Strange Forms Of Vitamins Called ‘Antivitamins’ May Fight Antibiotic-Resistant Superbugs. [online] ScienceAlert. Available at: <https://www.sciencealert.com/antivitamins-show-promise-in-tackling-our-growing-superbug-problem&gt; [Accessed 10 September 2020].

Berman, R., 2020. Shutting Down The Dance Of The Proteins. [online] Big Think. Available at: <https://bigthink.com/surprising-science/antivitamin-antibiotic?rebelltitem=2#rebelltitem2&gt; [Accessed 6 September 2020].

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