Small RNA molecule regulates the virulence factors of stomach bacteria

Over 50% of the global population carries the bacterium Helicobacter pylori in their stomach mucosa. While this bacterium does not generally cause problems in life, it can sometimes lead to inflammation, and in certain cases, may also lead to the development of stomach cancer.

Small RNA molecule regulates the virulence factors of stomach bacteria
Artistic representation of human stomach cells infected with Helicobacter pylori, showing the special Hummingbird cell shape induced by the bacterium. Image Credit: Chair of Molecular Infection Biology II/University of Würzburg/SCIGRAPHIX.

Several “virulence” factors are used by Helicobacter pylori that allow it to endure in the stomach which may lead to the development of disease. In the latest issue of the Molecular Cell journal, the research group of Professor Cynthia Sharma has reported that many of these factors are centrally governed by a small RNA molecule known as NikS.

Professor Sharma heads the Chair for Molecular Infection Biology II at Julius Maximilians University (JMU) Würzburg in Bavaria, Germany.

Among the target genes governed by the NikS molecule are the two most significant virulence factors of Helicobacter pylori and also two encoding outer membrane proteins. Particularly, the JMU team was able to demonstrate that the NikS molecule controls a bacterial oncoprotein called CagA protein that plays a vital role in the development of cancer induced by Helicobacter pylori. Additionally, a protein, whose function has remained unknown to date and is discharged into the environment by H. pylori, is also controlled by the NikS molecule.

The latest findings are applicable to infectious disease and medicine research.

With the knowledge of the different functions and underlying molecular mechanisms of this small RNA during infection and the associated bacterial signaling pathways, we can gain new targets for the development of novel antimicrobial strategies.”

Cynthia Sharma, Professor, University of Würzburg

Phase variation even in small RNA molecules

The fact that the bacterium H. pylori can successfully colonize such a hostile environment as the stomach can also be attributed to a unique genetic strategy: Similar to other pathogens, H. pylori employs a strategy called phase variation to adapt as flexibly as possible to variations in its environment.

The term “phase variation” means that the bacteria continuously and randomly switch the expression of a gene via genetic mutations, implying that certain bacteria in a population will invariably be prepared to express the significant gene when it becomes crucial—a kind of “bet-hedging” approach.

For the first time, Sharma’s group has been able to demonstrate that the expression of a small RNA molecule, like NikS, and not just of proteins, can also be exposed to phase variation. Based on the conditions prevailing in the stomach, varied amounts of the NikS molecule might be advantageous. The concentrations of the small RNA can alter to suit this through phase variation, thus leading to varied regulation of the disease-causing factors.

NikS helps to colonize host cells

This mechanism could play a major role in enabling Helicobacter pylori to adapt successfully to the variable stomach environment and thus chronically colonize its host.”

Cynthia Sharma, Professor, University of Würzburg

In experiments, Sharma’s group was able to demonstrate that NikS controls the internalization of the bacteria into host cells. The small RNA also makes it easier for the H. pylori bacterium to overcome epithelial obstacles and, therefore, may help access nutrients in the deeper tissues of the stomach more easily.

In additional studies, the JMU team is currently aiming to determine how the small RNA plays a role in the colonization of various niches present in the stomach and whether it controls other genes that may also be involved in the pathogenic properties of the bacterium.

Source:
Journal reference:

Eisenbart, S. K., et al. (2020) A repeat-associated small RNA controls the major virulence factors of Helicobacter pylori. Molecular Cell. doi.org/10.1016/j.molcel.2020.09.009.

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