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A Franco-Indian collaboration has identified an important mechanism involved in the transmission of antibiotic resistance, which is the principal cause of the failure of therapies aiming to eradicate Helicobacter pylori, a bacterium that infects half the world’s population. The results are published in Nature Communications on November 25, 2019.
The bacterium Helicobacter pylori infects the digestive system of half the world's population. This infection causes a whole series of pathologies ranging from gastritis and ulcers to gastric cancer. Since 1982, when this pathogen was identified as the etiological agent of ulcers, many patients have been treated with antibiotics to cure their illness and prevent cancer.
Nonetheless, in recent years we have seen a spectacular increase in the number of strains of H. pylori that are resistant to antibiotics. This is because the genome of this bacterium is incredibly plastic. Apart from the fact that it is highly mutagenic, the natural transformation of this pathogen plays a major role in the acquisition and propagation of genes that are resistant to antibiotics. Thanks to this, certain bacterial species are able to capture and incorporate DNA present in the environment into their genome.
In H. pylori, this process is extremely efficient, but very little is understood about the molecular machinery involved in capturing and internalizing transforming DNA.
A team from the François Jacob Institute of Biology (CEA/Université de Paris/Université Paris-Sud-Paris-Saclay), working with biochemists from the Institute for Integrative Biology of the Cell (CEA/CNRS/Université Paris-Sud-Paris-Saclay) and the Indian Institute of Science (Bangalore) has identified a key player in DNA internalization: the protein, ComH. Their research is published in Nature Communications on November 25, 2019.
ComH, which has no homology in other species, is present in the periplasm (1) of H. pylori. This protein has a strong affinity for binding with the DNA present in the direct environment of the bacterium. By interacting with a protein in the inner membrane pore, it then imports this transforming DNA into the cytoplasm (2).
Identifying this protein and its role in the process of the natural transformation of H. pylori opens up the possibility for a new treatment target to block the spread of the most virulent and antibiotic-resistant strains, with a view to eradicating infection linked to this pathogen worldwide.
It is now accepted that the Helicobacter pylori bacterium is the agent that causes stomach pathologies in humans: it causes chronic gastritis, gastric and duodenal ulcers, and it plays a key role in the genesis of gastric cancer (adenocarcinoma and lymphoma). Now thought of as an infectious disease, this has led to a change in how ulcers are treated and, more generally, has raised the hope that it might be possible to wipe out this bacterium (which infects 50% of the world's population) as a means of preventing gastric cancer.
H. pylori infection is one of the most widespread chronic infections in the world: 20 to 90% of adults are infected depending on the country in which they live. For any given country, the prevalence of this infection varies depending on the individual's social and economic status, the level of overcrowding and the sanitary conditions in which they live. The infection is more common in developing countries (80 to 90%) than in industrialized countries (25 to 30%). The bacterium is directly transmitted from person to person, mainly orally, and children are most usually infected via intrafamily transmission (mother to child, siblings). (Source: Institut Pasteur)
© Unité Technologie et Service Biolmagerie Ultrastructurale ( UTechS UBI) by Christine Schmitt and Olivier Gorgette
Identification of the periplasmic DNA receptor for natural transformation of Helicobacter pylori, Nature Communications, https://www.nature.com/articles/s41467-019-13352-6
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.