The bacteria that cause tuberculosis have evolved to use vitamin B12 from those infected to successfully develop the disease.

The journal Nature Communications includes the finding of researchers from the University of Zaragoza and the Aragón Health Research Institute, which demonstrates a direct relationship between tuberculosis and optimal levels of vitamin B12.

The work has been directed by Jesús Gonzalo Asensio, researcher of the Mycobacterial Genetics Group of Unizar and the IIS Aragón, and has been the objective of the doctoral thesis of Elena Campos Pardos

Researchers University of Zaragoza and the IIS Aragon they just demonstrated the direct relationship between tuberculosis and optimal levels of vitamin B12. Specifically, the magazine Nature Communications. publishes this finding that shows that the bacteria that cause tuberculosis have evolved to use vitamin B12 from those infected and be able to successfully develop the disease. These results open the doors to developing new therapeutic strategies to treat tuberculosis or other diseases.. In this sense, it is important to highlight that tuberculosis is today the deadliest infectious disease, causing more than 3.500 deaths daily, and surpassing more high-profile diseases such as COVID-19 in mortality.

The authors used for almost 10 years of research a broad collection of techniques from microbiology, genetic engineering, molecular biology, transcriptomics and proteomics to demonstrate that M. tuberculosis uses B12 to synthesize methionine, an essential amino acid for bacteria. The work has been directed by Jesus Gonzalo Asensio, researcher of the Mycobacteria Genetics Group of the University of Zaragoza and the IIS Aragon, and has been the objective of the doctoral thesis of Elena Campos Pardos.

La Vitamin B12 is a fundamental molecule for our metabolism, the formation of red blood cells and our neuronal functions. However, humans are not capable of synthesizing this molecule and we have to ingest it in the diet, hence its consideration as a vitamin. The only living beings capable of synthesizing vitamin B12 are some bacteria. that supply it to the food chain and ultimately reaches our food.

However, not all bacteria are capable of synthesizing vitamin B12. This work began in 2014 at the University of Zaragoza with the observation that the bacteria that cause tuberculosis have many mutations in their genes responsible for synthesizing said vitamin. This observation leads us to think that perhaps these bacteria are incapable of synthesizing B12. In a first experiment The researchers confirmed the inability to Mycobacterium tuberculosis -the bacteria that causes the disease- to synthesize its own vitamin, which led the research team to continue delving deeper into this study.

The fact that M. tuberculosis It has enzymes that need B12 for proper functioning, it seemed paradoxical to the researchers; hence The only possible explanation was that it could capture B12 from outside. In this sense, B12 would act as a vitamin for M. tuberculosis. This hypothesis was also demonstrated in the laboratory and opened the door to thinking that, in a real infection, the bacteria that cause tuberculosis could use vitamin B12 from infected people.

To demonstrate this, the team developed a model of B12 deficiency in mice. When the mice with a B12 deficiency were infected with M. tuberculosis, showed less pathology when compared to animals that show optimal levels of the vitamin. This demonstrates an antagonism between B12 deficiency and tuberculosis, something that was suggested in a landmark article published in 1933, and that researchers from the University of Zaragoza have demonstrated molecularly 91 years later.

In an attempt to demonstrate that tuberculosis bacteria have lost the ability to synthesize this vitamin during their evolution, researchers traced back to the oldest known ancestor of these bacteria, called M. canettii. Surprisingly, M. canettii is capable of synthesizing B12, and infection of mice with M. canettii showed no differences in pathogenesis regardless of the B12 levels of the infected mice. That's when researchers used their more than 20 years of genetic engineering experience to eliminate the ability to synthesize B12 in M. canettii, and the resulting bacteria showed a dependence on B12 in our mouse model equivalent to that of M. tuberculosis. These results demonstrate that the bacteria that cause tuberculosis today have evolved over thousands of years to do without the synthesis of B12, since this would be provided by their human host.

This work also reminds us of the antagonism between sickle cell anemia and the parasite that causes malaria. Other bacteria as Salmonella o Yersinia causing typhoid fever or bubonic plague, respectively, They could also use this mechanism of dependence on the B12 of their hosts.

Source: University of Zaragoza