Page 37 - Science

MICROBIOLOGY
Microbial warfare against viruses

Many new antiviral defense systems are found in bacteria and archaea

By Jin-Soo Kim 1,2 Many of these encode proteins that recog- It is of particular interest to find out how
nize nucleic acids, such as helicases and these systems recognize foreign compo-
I types: innate immune adaptive a consists of ognition and destruction of foreign genetic ner. Some of these systems may find use as
divided
nucleases, suggesting they have roles in rec-
nents, whatever they are, in a targeted man-
mmune
into two
systems are
innate
and
immunity.
system
The
molecular tools, like the well-known mem-
system
the
elements. Interestingly,
Zorya
components that are present in host or-
bers of the bacterial and archaeal immune
inner mem-
contains two
genes
encoding
brane proteins with flagellar motorlike do-
systems. Historically, microbial defense sys-
infection
pathogen
ganisms
by
before
and provides the first line of defense. For
membrane proteins may form a proton (H )
example, the restriction endonuclease system mains. Doron et al. speculate that these two tems have been successfully repurposed for
broad applications in research, medicine,
+
in prokaryotes degrades invader DNA (1). The channel to depolarize membrane potential and biotechnology. For example, restric-
adaptive immune system is activated after in- upon bacteriophage infection, leading to tion endonucleases cut DNA precisely in
fection and provides immunological memory cell death—a previously unknown mecha- vitro, enabling recombinant DNA technol-
and long-lasting protection against the same nism of antiviral defense in prokaryotes. ogy (5). More recently, genome editing has
pathogen. The CRISPR system captures Thoeris is another interesting system that been revolutionized by CRISPR–CRISPR-
a small piece of foreign DNA as a memory was identified by the enrichment of a gene associated (Cas) systems (6–9). Perhaps the
and recognizes and cleaves the same foreign family encoding the Toll-interleukin recep- microbial defense genes found by Doron et Downloaded from
DNA on reexposure (2), serving as adaptive tor (TIR) domain. The TIR domain is ubiqui- al. will lead to innovations and applications
immunity in prokaryotes. On page 1008 of tously found in innate immune systems such in biotechnology and medicine.
this issue, Doron et al. (3) unveil previously as the Toll-like receptor and interleukin-1 There are likely to be other unknown de-
unknown immune systems in bacteria and receptor of invertebrates and mammals and fense genes hiding in microbial genomes.
archaea against invading genetic elements, many pathogen-resistance proteins in plants Doron et al. might have missed bona fide
including plasmid DNA and bacteriophages (4). These TIR proteins recognize diverse antiviral genes that are poorly expressed in
(viruses that infect bacteria). Some of these the two model bacteria or that can protect
systems may provide powerful tools for bio- other host bacteria against bacteriophages http://science.sciencemag.org/
medical research and biotechnology, like re- not tested in this study. The 10 validated de-
striction endonucleases and CRISPR. fense systems are likely to be innate rather
Because genes in one immune defense sys- than adaptive immune systems, because
tem are often found next to genes in another adaptive immune systems like CRISPR
defense system, forming “defense islands” cannot be identified by a single round of
in microbial genomes, Doron et al. hypoth- phage infection or plasmid transformation.
esized that unknown defense systems could The study of Doron et al. will encourage re-
be found near already-known antiviral sys- searchers to search for microbial defense on March 1, 2018
tems. They computationally analyzed tens of genes and to investigate the molecular
thousands of genes in >45,000 bacterial and mechanisms of these defense systems. To do
archaeal genomes and found dozens of can- so, researchers will rely on molecular tools
didate defense gene families with unknown like CRISPR and on current and improved
functions in the vicinity of known defense methods of reading, writing, and editing
systems. To characterize these gene families, An electron microscopy image shows viruses genes and genomes. To rephrase Sydney
they expressed candidate genes in two het- (bacteriophage) surrounding a microbial cell. Brenner’s remarks, with respect, progress
erologous model bacteria, Escherichia coli in science is cyclic: new techniques leading
and Bacillus subtilis. These recombinant pathogen-associated molecular patterns to new discoveries, to new ideas, and then
bacteria were then challenged with a diverse (PAMPs) to trigger host immune responses. to new techniques again. j
set of bacteriophages. Remarkably, 9 of the Doron et al. suggest that the Thoeris TIR
REFERENCES AND NOTES
26 candidate systems conferred protection protein is an evolutionary ancestor of these
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2. M. Jinek et al., Science 337, 816 (2012).
al. named the nine gene families after leg- immune systems that are highly diverse, in- 3. S. Doron et al., Science 359, eaar4120 (2018).
endary guardians such as Zorya and Thoeris, nate immune systems are conserved across 4. J. A. Hoffmann et al., Science 284, 1313 (1999).
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and
PHOTO: AMI IMAGES/SCIENCE SOURCE a single gene or multiple (up to 14) genes. systems, the Wadjet system, named after an 7. P. Mali et al., Science 339, 823 (2013).
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6. S. W. Cho et al., Nat. Biotechnol. 31, 230 (2013).
of
either
systems consist
These
defense
8. L. Cong et al., Science 339, 819 (2013).
Egyptian goddess, failed to provide B. sub-
9. M. Jinek et al., eLife 2, e00471 (2013).
against
protection
10
tilis
bacteriophages
tested by Doron et al., but significantly re-
ACKNOWLEDGMENTS
1
Center for Genome Engineering, Institute for Basic Science,
duced transformation efficiency of plasmid
J.-S.K. is supported by the Institute for Basic Science
2
Seoul, Republic of Korea. Department of Chemistry, Seoul
(IBS-R021-D1).
DNA, suggesting that it may target foreign
National University, Seoul, Republic of Korea.
10.1126/science.aas9430
Email: jskim01@snu.ac.kr
SCIENCE sciencemag.org plasmid DNA, a molecular parasite. 2 MARCH 2018 • VOL 359 ISSUE 6379 993
Published by AAAS
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