They reveal the molecular mechanism that triggers the toxicity of cholera bacteria

Knowing the molecular mechanism that triggers a disease is essential to find new therapies. Cholera disease, caused by the bacteria Vibrio choleraeis not an exception.

A scientific team led by Miquel Collof the Institute for Research in Biomedicine (IRB Barcelona) and the Institute of Molecular Biology of Barcelona (IBMB-CSIC), in collaboration with researchers from the University of Detroit Mercy (USA), revealed the atomic structure of the ToxR protein, which is linked to the DNA of two promoters of the genes that cause virulence in the bacterium.

to bring the studypublished in PNAS, the scientists used X-ray diffraction techniquesusing synchrotron radiation, as well as artificial intelligence tools.

“ToxR is a protein known as ‘transcription factors’, which activates the toxT and ompU genes, causing, among other effects, the production of the cholera toxin It causes intense diarrhea and consequent dehydration, which can be fatal in a few days if not treated”, he says. coll.

ToxR is a protein that activates the toxT and ompU genes, causing production of the cholera toxin that causes severe diarrhea and subsequent dehydration, which can be fatal within days if left untreated.

Miquel Coll (IRB Barcelona)

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

“What we do know is that this transmembrane transcription factor, called ‘ToxR’, receives a signal when the bacteria arrives in the human intestine, as it detects bile salts. The signal is transduced, that is, transmitted, until it reaches the DNA inside the bacteria, triggering the toxicity cascade”, he explains. channelsfirst author of the research.

Virulence key activator

“The key activator of the virulence gene of Vibrio choleraeToxR, has been studied for years by several laboratories, but the exact way it interacts with DNA was a mystery until now.

This study demonstrates that ToxR recognizes DNA structure rather than specific DNA sequences, partly explaining its apparent promiscuous binding to DNA and revealing insights into its role in removing repressor proteins from virulence genes that impede the expression of factors such as the cholera toxin until the bacteria enter the host,” says Eric KrukonisUS team coordinator.

The forgotten pandemic

Cholera is a diarrheal disease caused by ingestion of contaminated food or water with the bacillus Vibrio cholerae. Although it has been eradicated in most developed countries, cholera remains 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 across much of the world from the Ganges delta in India.

This bacteria caused seven pandemics in the past, causing the death of millions of people on all continents. We are currently experiencing a new expansion of an infectious disease that is endemic in many developing countries and that mainly affects children.