Scientists discover how the toxicity of cholera bacteria is activated

Scientists from the Institute of Molecular Biology of Barcelona (IBMB-CSIC), from the Institute for Research in Biomedicine (IRB), both in Barcelona (Spain) and the University of Detroit Mercy (USA.) have discovered how the toxicity of the bacterium of the angerwhich can be very useful to find new treatments.

The research, published in the journal PNAS, has revealed that the structure of a protein bound to DNA activates various genes that regulate the toxicity and virulence of the bacterium ‘Vibrio cholerae’which causes cholera.

The work, directed by Miquel Coll, has revealed the atomic structure of the ToxR protein, which is linked to the DNA of two promoters of the genes that cause the virulence of the bacteria.

To carry out the study, the scientists have used X-ray diffraction techniques, using synchrotron radiation, and artificial intelligence tools.

“ToxR is a protein of the so-called ‘transcription factors’, which activates the toxT and ompU genes, causing, among other effects, the production of cholera toxin that causes severe diarrhea and consequent dehydration, which can be fatal in a few days. if not treated”Coll detailed.

This finding reveals that ToxR binds to multiple regulatory sequences in bacterial DNA, either in tandem or inverted, in turn capturing RNA polymerase, the molecular machine that transcribes genes.

“What we know is that this transmembrane transcription factor, called ToxR, receives a signal when the bacterium reaches the human intestine, since it detects bile salts. The signal is transmitted until it reaches the DNA inside the bacterium, triggering the cascade of toxicity”specified the researcher Albert Canals.

According to the researchers, the key activator of the Vibrio cholerae virulence gene, ToxR, has been studied for years by various laboratories, but the exact way in which it interacts with DNA was a mystery until now.

Cholera is a diarrheal disease caused by ingestion of food or water contaminated with the bacillus. ‘Vibrio cholerae’and, although it has been eradicated in a large part of developed countries, it continues to be a threat to public health in countries with poor sanitary conditions, as well as an indicator of inequality and lack of social development.

According to the World Health Organization (WHO), during the 19th century, cholera spread through much of the world from the Ganges delta in India.

This bacterium has caused up to seven pandemics in the past, causing the death of millions of people on all continents.

Currently, there is a seventh pandemic of this infectious disease that is endemic in many developing countries and affects especially children.

During the year 2022, a total of 29 countries reported cholera cases, including Haiti, Malawi, Yemen and Syria, which reported large epidemic outbreaks.

According to the researchers, the increase in cases worldwide has grown in recent years, and they are becoming more numerous, more widespread, and more serious, due, in large part, to climate change that causes floods, droughts, and massive migrations.

War conflicts and natural catastrophes also limit drinking water and facilitate the spread of disease.

Source: EFE