Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

When bacteria get the flu and sharpen their knives

31.03.2011
Scientists identify a novel pathway to activate the bacterial immune system

It is true; also microbes get infected by viruses. Consequently, they have evolved immunity mechanisms to fend off attacks by the enemy. In bacteria and archaea CRISPR/Cas has recently been discovered as a novel immune system to fight alien genomes. The system, which is also known as prokaryotic RNA interference, consists of proteins and short RNA molecules (crRNAs) that target the intruders for destruction.

A key event in the activation of the system is the maturation of crRNAs. Joint research led by scientists in Umeå, Sweden in collaboration with colleagues in Würzburg, Germany, revealed a new pathway, which allows bacteria to activate the crRNAs to block the entry of enemy genomes. The results are now published in the prestigious scientific journal Nature.

During their lifetime, microbes are constantly and heavily facing assaults by viruses known as phages or invading circular nucleic acid strands known as plasmids. On the one hand, these alien genomes can be detrimental for the microbial host; for example, lytic phages that destroy the microbes upon infection. On the other hand, foreign DNA such as plasmids can endow microbes with new genes to resist antibiotic action.

To protect themselves against infection by the enemy, microbes have invented a sophisticated defence mechanism. CRISPRs (for Clustered Regularly Interspaced Short Palindromic Repeats) are genetic islets in the microbial genome that consist of genes encoding the CRISPR-associated (Cas) proteins and an array of unique enemy-targeting elements, called spacers, interspaced by repeat sequences. The system is quite complex and has evolved into various subtypes that differ in the combination of Cas genes and in the number of spacers-repeats in the array.

All steps of the immune system require the activities of the Cas proteins that are thought to be sufficient for CRISPR activation and function. The latest research on CRISPR reported in the journal Nature in a paper titled ”CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III” demonstrates a fundamentally novel pathway that requires additional factors from the host machinery to activate CRISPR, evocative of the eukaryotic RNA interference system.

How does CRISPR/Cas work? When bacteria and archaea are exposed to viruses or plasmids, short pieces of DNA from the alien genomes are injected into the host cell and incorporated into the CRISPR spacer-repeat array on the chromosome. This genomic manipulation leads to reprogramming of the microbial host cell, which then uses the newly inserted DNA as a memory device of previously encountered alien genomes to provide specific immunity against future attacks by the same elements. In the following process, crRNA maturation, the host cell transcribes the CRISPR spacer-repeat array into an RNA molecule that gets diced into short mature RNAs (crRNAs) of unique truncated spacer-repeat sequences. In the last step, the silencing of the alien genome, the crRNAs target the invading genomes in a sequence-specific manner leading to destruction of the foreign genetic material.

The CRISPR/Cas pathway is only been studied for less than a decade and many details around its regulation and mechanisms are still unclear. New light is now shed on the activation of the crRNAs by the research team around Emmanuelle Charpentier at the Laboratory for Molecular Infection Medicine Sweden (MIMS) in Umeå, Sweden with her former team at the Max F. Perutz Laboratories in Vienna, Austria in collaboration with the research group of Jörg Vogel at the Institute for Molecular Infection Biology (IMIB) at the University of Würzburg, Germany.

“We have analyzed the CRISPR/Cas pathway in our model organism Streptococcus pyogenes, a human pathogen”, says Emmanuelle Charpentier, who led the study. “Unexpectedly, we have discovered a novel pathway of CRISPR activation involving the concerted action of three new factors to maturate the “crispy” crRNAs: a small RNA molecule, the endoribonuclease III from the bacterial host and a novel Cas protein (Csn1). The mechanism is particularly neat. The small RNA molecule, called tracrRNA, pairs specifically with the CRISPR precursor RNA at the level of each of the repeats. The duplexes formed are then recognized by an enzyme, the endoribonuclease III of the bacterial host, that dices the RNAs in the presence of the Cas protein Csn1, leading to the production of the shorter crRNAs”.

In eukaryotes, Dicer and Drosha are enzymes of the endoribonuclease III family and are responsible for the production of small interfering RNAs and maturation of microRNAs. “As such, the requirement for the bacterial endoribonuclease III to mature the crRNAs is reminiscent of the RNA interference pathway in eukaryotes“, Charpentier says. “Our findings of the first host factors recruited to CRISPR/Cas highlights the remarkable evolutionary diversification of CRISPR/Cas systems. The discovery raises also the exciting possibility that additional factors from the microbial host cell – outside CRISPR/Cas – might be involved in the other steps of the immune system.”

“The pathway functions to protect bacteria from killing by lytic phages” Charpentier continues, “but in addition, we show that CRISPR can also target viruses of the so-called lysogenic phage family that are known to transfer virulence genes among streptococcal clinical isolates. Targeting of virulence genes highlights a novel biological function for CRISPR and underlines an alternative mechanism to modulate the pathogenic potential of bacterial clinical isolates.”

Charpentier ends: “Finally, manipulation of the novel discovered pathway could lead to novel ways of specifically silencing targeted genes. Novel RNA-based interference approaches can have useful implications either to genetically engineer modified microbes for research studies or to generate bacterial strains resistant to destructive viruses. This could help maintain microbe stability in dairy food production”.

This work was supported in part by funding from the Swedish Research Council, Umeå University, the Austrian Science Fund, the German Research Council, the German Ministry for Education and Science, and the European Community.

The Laboratory for Molecular Infection Medicine Sweden, MIMS, is the Swedish node of the Nordic EMBL Partnership for Molecular Medicine. The institute is dedicated to research on the molecular mechanisms of infections and the development of new antimicrobial strategies. MIMS is part of the research consortium Umeå Centre for Microbial Research, UCMR. Visit: http://www.mims.umu.se and http://www.ucmr.umu.se.

The Institute for Molecular Infection Biology (IMIB) is an interdisciplinary institution at the Medical Faculty of the University of Würzburg. Members of the institute are interested in biological problems of pathogens and infectious diseases, with an emphasis on molecular mechanisms. Visit: http://www.infektionsforschung.uni-wuerzburg.de

Additional Information: For more information, please contact:

Dr. Emmanuelle Charpentier
The Laboratory for Molecular Infection Medicine Sweden, MIMS
and the Umeå Centre for Microbial Research UCMR
Umeå University, SE-90187 Umeå
emmanuelle.charpentier@mims.umu.se
http://www.mims.umu.se; http://www.ucmr.umu.se
Original publication:
Elitza Deltcheva, Krzysztof Chylinski, Cynthia M. Sharma, Karine Gonzales, Yanjie Chao, Zaid A. Pirzada, Maria R. Eckert, Jörg Vogel & Emmanuelle Charpentier: CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III. Nature 31 March 2011. (doi:10.1038/nature09886)

Eva-Maria Diehl | idw
Further information:
http://www.infektionsforschung.uni-wuerzburg.de

More articles from Life Sciences:

nachricht Unique genome architectures after fertilisation in single-cell embryos
30.03.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

'On-off switch' brings researchers a step closer to potential HIV vaccine

30.03.2017 | Health and Medicine

Penn studies find promise for innovations in liquid biopsies

30.03.2017 | Health and Medicine

An LED-based device for imaging radiation induced skin damage

30.03.2017 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>