How is the toxicity of the cholera bacteria activated?

scientists from Institute of Molecular Biology in Barcelona (IBMB-CSIC)from Institute for Biomedical Research (IRB)both in Barcelona (Spain) and from the USAUniversity of Detroit Mercy (USA) discovered how the toxicity of the cholera bacterium is activated, which can be very useful for finding new treatments.

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

Work, led Miquel Colldiscovered the atomic structure of the protein ToxR, which is associated with the DNA of two gene promoters that cause the bacteria’s virulence.

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

“ToxR is a so-called ‘transcription factor’ protein, which activates the toxT and ompU genes, causing, among other things, the production of cholera toxin that causes severe diarrhea and consequent dehydration, which can be fatal within days . . . if untreated,” he said. is Coll.

This discovery reveals that ToxR binds to multiple regulatory sequences in bacterial DNA, either in tandem or inverted, in turn trapping 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 a toxicity cascade,” explained researcher Albert Canals. .

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

Cholera is a diarrheal disease caused by ingestion of food or water contaminated with cholera. bacillus ‘Vibrio cholerae’, and, although it has been eradicated in a large part of developed countries, it is still 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 World Health Organization (WHO)During the 19th century, cholera spread from the Ganges delta in India to most of the world.

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

Currently, the seventh pandemic of this infectious disease is underway, which is endemic in many developing countries and affects children in particular.

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

According to scientists, the number of patients around the world has increased in recent years and they are becoming more numerous, more widespread and more serious, largely due to climate changes that cause floods, droughts and mass migrations.

Conflicts of war and natural disasters also limit drinking water and facilitate the spread of disease.

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