Publication Date:
2013-04-16
Description:
CRISPR/Cas (clustered regularly interspaced palindromic repeats/CRISPR-associated) systems are a bacterial defence against invading foreign nucleic acids derived from bacteriophages or exogenous plasmids. These systems use an array of small CRISPR RNAs (crRNAs) consisting of repetitive sequences flanking unique spacers to recognize their targets, and conserved Cas proteins to mediate target degradation. Recent studies have suggested that these systems may have broader functions in bacterial physiology, and it is unknown if they regulate expression of endogenous genes. Here we demonstrate that the Cas protein Cas9 of Francisella novicida uses a unique, small, CRISPR/Cas-associated RNA (scaRNA) to repress an endogenous transcript encoding a bacterial lipoprotein. As bacterial lipoproteins trigger a proinflammatory innate immune response aimed at combating pathogens, CRISPR/Cas-mediated repression of bacterial lipoprotein expression is critical for F. novicida to dampen this host response and promote virulence. Because Cas9 proteins are highly enriched in pathogenic and commensal bacteria, our work indicates that CRISPR/Cas-mediated gene regulation may broadly contribute to the regulation of endogenous bacterial genes, particularly during the interaction of such bacteria with eukaryotic hosts.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651764/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651764/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sampson, Timothy R -- Saroj, Sunil D -- Llewellyn, Anna C -- Tzeng, Yih-Ling -- Weiss, David S -- R56 AI061031/AI/NIAID NIH HHS/ -- R56 AI087673/AI/NIAID NIH HHS/ -- R56-AI061031/AI/NIAID NIH HHS/ -- R56-AI87673/AI/NIAID NIH HHS/ -- U54 AI057157/AI/NIAID NIH HHS/ -- U54-AI057157/AI/NIAID NIH HHS/ -- England -- Nature. 2013 May 9;497(7448):254-7. doi: 10.1038/nature12048. Epub 2013 Apr 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Microbiology and Molecular Genetics Program, Department of Microbiology and Immunology, Emory University, Atlanta, Georgia 30329, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23584588" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Female
;
Gammaproteobacteria/genetics/*immunology/metabolism/*pathogenicity
;
Genes, Bacterial/genetics
;
Host-Pathogen Interactions/immunology
;
*Immune Evasion
;
Immunity, Innate/*immunology
;
Mice
;
Mice, Inbred C57BL
;
Phylogeny
;
RNA, Bacterial/genetics/metabolism
;
Time Factors
;
Toll-Like Receptor 2/immunology/metabolism
;
Virulence/genetics
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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