Small RNA as a central player in infections

Date:
October 15, 2020
Source:
University of Wu"rzburg
Summary:
The most important pathogenicity factors of the gastric pathogen
Helicobacter pylori are centrally regulated by a small RNA molecule,
NikS. And this was not the only surprise that NikS provided.



FULL STORY ==========================================================================
More than half of the world's population carries the bacterium
Helicobacter pylori in their stomach mucosa. It often causes no problems throughout life, but sometimes it can cause inflammation, and in some
cases, it can even lead to the development of stomach cancer.


========================================================================== Helicobacter pylori uses several "virulence" factors that allow it to
survive in the stomach and can lead to the development of disease. In this issue of the journal Molecular Cell, Professor Cynthia Sharma's research
team report that multiple of these factors are centrally regulated
by a small RNA molecule called NikS. Prof. Sharma heads the Chair for
Molecular Infection Biology II at Julius-Maximilians-Universita"t (JMU) Wu"rzburg in Bavaria, Germany.

Among the target genes regulated by NikS are the two most important
virulence factors of Helicobacter pylori as well as two encoding outer
membrane proteins.

In particular, the JMU researchers were able to show that NikS regulates
the CagA protein, a bacterial oncoprotein that plays a central role in the development of cancer instigated by Helicobacter pylori. In addition,
a protein with a so far unknown function that is released into the
environment by H.

pylori is also under the control of NikS.

The new findings are relevant for medicine and infectious disease
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," explains Cynthia Sharma.

Phase variation even in small RNA molecules The fact that Helicobacter
pylori can colonize such a hostile environment as the stomach so
successfully is also due to a special genetic strategy: Like other
pathogens, H. pylori uses a strategy known as phase variation to adapt
as flexibly as possible to changes in its environment. Phase variation
means that the bacteria constantly switch expression of a gene at random through genetic mutations, meaning that some bacteria in a population will always be ready to express the important gene when it becomes important --
a sort of "bet-hedging" strategy.

Sharma's team has now been able to show for the first time that
the expression of a small RNA molecule such as NikS, and not just
of proteins, can also be subject to phase variation. Depending on
the conditions prevailing in the stomach, different amounts of NikS
might be beneficial. Levels of the small RNA can change to suit this
through phase variation, thereby leading to different 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," says
Sharma. In experiments, her team was able to show that NikS influences
the internalization of the bacteria into host cells. In addition, the
small RNA makes it easier for H. pylori to overcome epithelial barriers
and, thus, might lead to better access of nutrients in deeper tissues
in the stomach.

In further studies, the JMU researchers now aim to find out how the small
RNA contributes to the colonization of different niches in the stomach
and whether it regulates other genes that might also be involved in the bacterium's pathogenic properties.


========================================================================== Story Source: Materials provided by University_of_Wu"rzburg. Original
written by Robert Emmerich. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Sara K. Eisenbart, Mona Alzheimer, Sandy R. Pernitzsch, Sascha
Dietrich,
Stephanie Stahl, Cynthia M. Sharma. A Repeat-Associated Small
RNA Controls the Major Virulence Factors of Helicobacter
pylori. Molecular Cell, 2020; DOI: 10.1016/j.molcel.2020.09.009 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/10/201015092431.htm

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