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<h2 class="element-invisible">You are here</h2><div class="breadcrumb"><a href="/">Home</a> » <a href="/news-events">News & Events</a> » <a href="/news-events/nih-research-matters">NIH Research Matters</a></div> <div class="l-region l-region--section-header">
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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2014-09-29T00:00:00-04:00" class="date-display-single">September 29, 2014</span></p><div class='syndicate'><h1>Method Can Target Specific Microbes</h1><div class="callout callout-with-border"><h3>At a Glance</h3>
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<ul class="spaced">
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<li>Scientists designed a way to target and destroy specific DNA sequences in microbes, thus removing harmful bacterial genes.</li>
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<li>The approach might be used to develop therapies against pathogenic bacteria, including those resistant to multiple antibiotics.</li>
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2014/bacteriophages.jpg?itok=sLfUw3Cp&timestamp=1430404672 1x" media="screen and (min-width: 800px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/research-matters/2014/bacteriophages.jpg?itok=4NF-LGRV&timestamp=1430404672 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/research-matters/2014/bacteriophages.jpg?itok=b1s1uplh&timestamp=1430404672 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2014/bacteriophages.jpg?itok=3SiG5081&timestamp=1430404672 1x" media="screen and (min-width: 0)" />
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</picture><span class="caption">Bacteriophages (pictured) can be used to deliver the CRISPR-Cas system into bacterial cells.</span><span class="credit">David Gregory and Debbie Marshall, Wellcome Images. All rights reserved by Wellcome Images.</span></div>
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</div><p>Over time, many bacteria have adapted to the drugs designed to kill them, making antibiotics less effective. Diseases such as tuberculosis, gonorrhea, and a variety of healthcare-associated infections are now difficult to treat when they’re caused by multidrug-resistant bacteria. New approaches are needed to address this growing problem.</p>
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<p>Antibiotics work by disrupting bacteria’s ability to grow and replicate. These drugs tend to be broad spectrum, affecting both beneficial and harmful bacteria. Dr. Timothy K. Lu at the Massachusetts Institute of Technology, with graduate students Robert Citorik and Mark Mimee, set out to develop a way to specifically target harmful bacteria.</p>
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<p>Bacteria have evolved systems to protect themselves against invaders. One of these, the CRISPR-Cas immune system, features clusters of short, repeated DNA sequences separated by other short stretches called spacers. These spacer sequences are created from the genetic material of bacteriophages (viruses that attack bacteria) and plasmids (pieces of DNA exchanged between bacteria) that the cell or an ancestor encountered. The spacers provide immunity to future exposure by directing enzymes called nucleases—encoded by <em>cas</em> (CRISPR-associated) genes—to destroy those specific genetic sequences.</p>
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<p>The researchers reasoned that they could modify the spacers to target specific genetic sequences associated with bacterial virulence or antibiotic resistance. The work was funded in part by an NIH Director’s New Innovator Award and NIH’s National Institute of General Medical Sciences (NIGMS). Results appeared online on September 21, 2014, in <em>Nature Biotechnology.</em></p>
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<p>The team used a CRISPR-Cas system to successfully target antibiotic resistance genes in <em>E. coli</em>. Components of the system could be delivered either by bacteriophages or by other bacteria via conjugation (a process by which bacteria exchange genetic material). Both effectively spread through <em>E. coli</em> populations. The system could target genes on bacterial chromosomes or plasmids.</p>
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||
<p>The team also tested whether they could target a known virulence factor that allows the pathogen <em>E. coli</em> O157:H7 to colonize intestines. Using bacteriophage to deliver a CRISPR-Cas system against the gene, they saw a 20-fold reduction in viable <em>E. coli</em> cells. The team tested this system in greater wax moth larvae, an infection model often used to predict virulence in mammals. The system significantly improved survival in larvae infected with <em>E. coli</em> O157:H7.</p>
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<p>The researchers were able to target multiple resistance genes at once by including 2 spacers with DNA from 2 different antibiotic resistance genes. In addition, the system could discriminate between targets that differed by only a single nucleotide. Finally, the team showed that the system could be used to selectively kill a specific <em>E. coli</em> strain in a population based on its genetic content while leaving others untouched.</p>
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<p>“This is a pretty crucial moment when there are fewer and fewer new antibiotics available, but more and more antibiotic resistance evolving,” Lu says. “We've been interested in finding new ways to combat antibiotic resistance.” The researchers are now working to further improve delivery of the CRISPR-Cas system components.</p>
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<p>—by Harrison Wein, Ph.D.</p>
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</div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="https://www.nih.gov/news-events/nih-research-matters/molecular-insights-into-target-multidrug-resistance" target="_top">Molecular Insights into a Target for Multidrug Resistance</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/method-quickly-assesses-antibiotics" target="_top">Method Quickly Assesses Antibiotics</a></li><li><a href="https://newsinhealth.nih.gov/issue/Feb2014/Feature1" target="_top">Stop the Spread of Superbugs — Help Fight Drug-Resistant Bacteria</a></li><li><a href="http://www.niaid.nih.gov/topics/antimicrobialresistance/Pages/default.aspx" target="_top">Antimicrobial (Drug) Resistance</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="http://www.ncbi.nlm.nih.gov/pubmed/25240928">Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases.</a> Citorik RJ, Mimee M, Lu TK. <em>Nat Biotechnol</em>. 2014 Sep 21. doi: 10.1038/nbt.3011. [Epub ahead of print]. PMID: 25240928.</p><p class="footnote"><strong class="label-inline">Funding: </strong>An NIH Director’s New Innovator Award and NIH’s National Institute of General Medical Sciences (NIGMS); the Defense Threat Reduction Agency; US Army Research Laboratory; the US Army Research Office; Henry L. and Grace Doherty Professorship in Ocean Utilization; Howard Hughes Medical Institute; and Fonds de recherche Santé Québec.</p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/brain-changes-observed-during-pregnancy">Brain changes observed during pregnancy</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-detecting-cancer">Research in Context: Detecting cancer</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/risk-future-burden-dementia-united-states">Risk and future burden of dementia in the United States </a></p>
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||
|
||
<p><a href="https://www.nih.gov/news-events/nih-research-matters/complete-wiring-map-adult-fruit-fly-brain">Complete wiring map of an adult fruit fly brain</a></p>
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<h3 class="block__title">About NIH Research Matters</h3>
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<p><strong>Editor:</strong> Harrison Wein, Ph.D.</p>
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<p><strong>Assistant Editors:</strong> Vicki Contie and Brian Doctrow, Ph.D.</p>
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<p><strong><em>NIH Research Matters </em></strong>is a weekly update of NIH research highlights reviewed by NIH’s experts. It's published by the <a href="/institutes-nih/nih-office-director/office-communications-public-liaison">Office of Communications and Public Liaison</a> in the <a href="/institutes-nih/nih-office-director">NIH Office of the Director</a>.</p>
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<p>ISSN 2375-9593</p>
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