Helicobacter pylori, a stomach germ, knows how to protect itself against attacks by the immune system or by antibiotics. A research team from the University of Würzburg has succeeded in deciphering new details of this ability.
Helicobacter pylori is widespread worldwide. Experts estimate that about half of humanity carries the bacterium — preferably in the stomach. Thanks to various adaptations, Helicobacter is protected from the extremely acidic environment and is able to settle and multiply permanently in the gastric mucosa. Above all, the ability to make the structures on the surface of its envelope extremely variable helps the bacterium to hold its own in this environment, which is hostile in and of itself. It uses the same trick to hide itself from the immune system of its host.
A group of scientists from the Julius Maximilian University of Würzburg (JMU), together with collaborators at the Institut Pasteur in Paris, have now uncovered new details about how it does this. The team has succeeded in identifying a gene that is involved in the synthesis of the surface structures of the bacteria.
Furthermore, they were able to show that a small RNA can modulate the expression of this gene and thus vary the nature of the surface structures. In this way, Helicobacter pylori not only manages to escape the immune system, but also to vary its sensitivity to certain antibiotics.
Publication in Nature Communications
The researchers have now published the results of their investigations in the journal Nature Communications. Cynthia Sharma, head of the Department of Molecular Infection Biology II and spokesperson for the Center for Infection Research at JMU, is responsible for the publication.
Lipopolysaccharides (LPS): This is the technical term for these surface structures in which Sharma and her team are interested. These are compounds of fat-like (lipo) components and sugar (polysaccharide) that are found in the outer membrane of bacteria such as Helicobacter. “Helicobacter pylori produces a unique lipopolysaccharide compared to other bacteria that performs important functions in the infection process. Without this molecule, the bacterium could not colonize the human stomach or survive there permanently,” Sharma explains.
On the other hand, LPS is one of the most powerful stimulators of the immune system. For an organism to effectively fight an infection with Helicobacter, its immune cells must be able to recognize these structures. The bacteria have learned to prevent this in the course of evolution: “During an infection, many pathogens modify their LPS synthesis as well as their structure. In this way, they can escape recognition by the immune system,” says Sharma.
Widely dispersed genes
Although the central role of lipopolysaccharides in the successful infection of the host by certain bacteria is well known, the synthetic pathway of these molecules in the case of Helicobacter pylori has not yet been completely deciphered. “This could be due to the fact that the genes responsible for LPS synthesis are scattered throughout the bacterium’s genome,” Sharma suspects. Together with her team, she has now succeeded in identifying an essential protein in this process.
So-called “hypervariable simple sequence repeats (SSRs)” are one of the main sources of the changes in lipopolysaccharides. They are short DNA sequences that are randomly varied in length during cell division and influence the expression of genes. In previous work, the group was able to show that such SSRs are also targets for small regulatory RNAs (sRNAs), an important class of regulators that, for example, control gene expression under stress conditions or during infection.
Gradual resistance to antibiotics
In the study now published, the participants show that a specific sRNA with the scientific name RepG (regulator of polymeric G‑repeats) in Helicobacter pylori controls the synthesis of LPS by modulating the expression of a gene that is important for this process. The interplay between the various players allows for stepwise control of LPS biosynthesis by the sRNA.
“In this way, regulatory RNA can fine-tune the structure of lipopolysaccharides, influencing their sensitivity to antibiotics and reducing the risk of being recognized by the host immune system.”
- Sandy Westermann, first author of the study
