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 New application for acoustics helps estimate marine life populations
16.01.2018 | University of California - San Diego

nachricht Unexpected environmental source of methane discovered
16.01.2018 | University of Washington Health Sciences/UW Medicine

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

Im Focus: A thermometer for the oceans

Measurement of noble gases in Antarctic ice cores

The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

White graphene makes ceramics multifunctional

16.01.2018 | Materials Sciences

Breaking bad metals with neutrons

16.01.2018 | Materials Sciences

ISFH-CalTeC is “designated test centre” for the confirmation of solar cell world records

16.01.2018 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>