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A collaborative work headed by LRIG (IRCM) has uncovered a protein that is essential for an antibiotic resistance propagation pathway in the bacterium
Helicobacter pylori. The results, published in
Nature Communications, shed light on a potential therapeutic target in the battle against gastric infection.
The bacterium Helicobacter pylori infects the internal lining of the stomach. Infection usually occurs during infancy and persists for life if not treated. In some people, H. pylori infection is symptomless, but in others it leads to such pathologies as chronic gastritis, duodenal ulcers and even stomach cancer. Overall, about half of the world's population is carrying H. pylori, but infection rates vary geographically. For example, they range from 60 to 90% in Africa, Asia and Latin America, but from 30 to 40% in Europe.
Since 1982, when H. pylori was identified as their cause, ulcers have been curatively treated with antibiotics, which thus prevents their progression toward cancer. However, due to the impressive plasticity of its genome, the last few years have seen a spectacular increase in H. pylori strains resistant to antibiotics. Beyond its high rate of mutagenesis, the bacterium can acquire antibiotic resistance from a process called natural transformation. This latter describes the ability of certain bacteria to capture and incorporate in their own genomes any DNA present in their immediate environment, including genetic material - and the advantages that may come with it - released by other bacteria. H. pylori is a particularly proficient natural transformer, but the molecular machinery it uses for the process is largely unknown.
Researchers from IRCM's Laboratory of Genetic Instability Research (LRIG), in partnership with teams from I2BC (Gif-sur-Yvette, Frédéric Joliot Institute for Life Sciences/CEA Paris-Saclay) and the Indian Institute of Sciences (Bangalore), recently contributed greatly to resolving this mystery with the identification of ComH, an essential protein in the chain of events leading to the internalization of DNA by H. pylori.
ComH, which is unknown in other bacteria, is a periplasmic protein, i.e., situated between the bacterium's outer and inner membranes. It binds strongly to DNA, then interacts with elements of ComEC, an inner membrane protein responsible for the transfer of transforming DNA into the bacterial cytoplasm. This transfer of genetic material by H. pylori during natural transformation is important for both its virulence and antibiotic resistance.
The identification of a protein uniquely present in H. pylori and furthermore essential to its natural transformation opens new doors toward the identification of a therapeutic target and the elimination of the infection.
These results have been shared through a press release.
Identification of the periplasmic DNA receptor for
natural transformation of Helicobacter pylori I Nature Communications
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.