Philippe Horvath talks with
ScienceWatch.com and answers a few questions about
this month's New Hot Paper in the field of
Microbiology. The author has also sent along images of
Article Title: CRISPR provides acquired resistance
against viruses in prokaryotes
Authors: Barrangou, R;Fremaux, C;Deveau, H;Richards,
M;Boyaval, P;Moineau, S;Romero,
Year: MAR 23 2007
* Danisco France SAS, Boite Postale 10, F-86220 Dange St
* Danisco France SAS, F-86220 Dange St Romain,
(addresses have been truncated)
Why do you think your paper is highly
Our work provides the first biological evidence showing that CRISPR
(Clustered Regularly Interspaced Short Palindromic Repeats), along with
CRISPR-associated (cas) genes, functions as a new antiviral system
in prokaryotes. Discovered fortuitously in 1987, and described as a
widespread family of prokaryotic DNA repeats in 2002, CRISPRs have gained
considerable interest in 2005-2006 when distinct publications hypothesized
a role in cellular defense against invading DNA.
The popularity of CRISPR is undoubtedly linked to its putative mechanism of
action, which is probably analogous to RNA interference (RNAi).
Furthermore, in contrast to the eukaryotic immune system based on antigens,
the acquired CRISPR immunity is based on nucleic acids.
However, prior hypotheses were based on in silico observations,
and remained purely theoretical until the publication of our paper. Our
experimental results on Streptococcus thermophilus combine biology
of viral-host interactions, genetic engineering of CRISPR/cas
structures for demonstration purposes, and CRISPR sequence comparison
across a large number of bacterial strains.
Does it describe a new discovery, methodology, or
synthesis of knowledge?
Our paper represents the first demonstration of the functionality of
CRISPR/cas as a new microbial immune system. It is essentially the
validation of a putative hypothesis. This achievement is mostly due to the
concomitant availability, within Danisco, of two large and complementary
collections: bacterial strains and their corresponding bacterial viruses.
Would you summarize the significance of your paper
in layman's terms?
Bacteria and bacterial viruses (bacteriophages, or phages) behave like prey
and predators in a ruthless fight. Since the dawn of time bacteria have
developed a variety of resistance mechanisms against viral infection. In
response, phages continuously evolve wily strategies to skirt around
Our results show for the first time that a peculiar structure previously
identified within bacterial genomes constitutes a new antiviral system.
CRISPR structures can be seen as an archive of past encounters, where the
bacterium stores short fragments of viral genomes. The presence of these
viral fragments provides to the bacterium a kind of immunity against any
forthcoming virus containing the same fragment.
Our discovery opens new perspectives in the fight against viruses, notably
in the field of microbial food fermentations (dairy, meat, and wine
industries, for instance). It could also impact our use of viruses to fight
against undesirable bacteria (phage therapy), an approach that is currently
considered as a credible alternative to antibiotics.
How did you become involved in this research, and
were there any problems along the way?
Danisco is a world-leading company for food ingredients. In order to
provide starter cultures with enhanced robustness, Danisco Innovation
explores any new track that could improve our knowledge on bacterial
resistance against phages. Our interest for CRISPR goes back to 2002, while
we were involved in the genome sequencing projects for Lactobacillus
acidophilus NCFM® and Streptococcus
thermophilus LMD-9 (a Danisco strain). Shortly after having discovered
CRISPR structures in these two genomes, the analysis of CRISPR arrays
across a diversity of bacterial strains from the same species suggested
unambiguously a link with phage resistance. Experiments were then designed
to test our hypotheses.
Where do you see your research leading in the
Based on the knowledge we have added on CRISPR, we are actively
implementing this strategy and we now concentrate our efforts on the
development of natural approaches that will provide, in a near future, new
starter cultures for the food industry. Our initial publication on CRISPR
has also opened new doors to collaborations with academic teams across the
Do you foresee any social or political
implications for your research?
Our research does not have any social nor political implication.
Nevertheless, in addition to improving the quality of functional food
ingredients, it should have a significant impact on the population
Danisco France SAS
Keywords: CRISPR, Clustered Regularly Interspaced Short
Palindromic Repeats, CRISPR-associated, cas, CRISPR/cas structures,
prokaryotes, prokaryotic DNA, RNA interference, RNAi, microbial food
fermentations, undesirable bacteria, phage therapy, Lactobacillus
acidophilus NCFM, Streptococcus thermophilus LMD-9, Danisco strain,