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1、ARTICLEdoi:10.1038/nature09523TheCRISPR/CasbacterialimmunesystemcleavesbacteriophageandplasmidDNA111223JosianeE.Garneau,Marie-E`veDupuis,ManuelaVillion,DennisA.Romero,RodolpheBarrangou,PatrickBoyaval,3311ChristopheFremaux,PhilippeHorvath,AlfonsoH.Magada´n&SylvainMoineauBacteriaandArchaeahaved
2、evelopedseveraldefencestrategiesagainstforeignnucleicacidssuchasviralgenomesandplasmids.Amongthem,clusteredregularlyinterspacedshortpalindromicrepeats(CRISPR)locitogetherwithcas(CRISPR-associated)genesformtheCRISPR/Casimmunesystem,whichinvolvespartiallypalindromicrepeatsseparatedbyshortstretc
3、hesofDNAcalledspacers,acquiredfromextrachromosomalelements.Itwasrecentlydemonstratedthatthesevariablelocicanincorporatespacersfrominfectingbacteriophagesandthenprovideimmunityagainstsubsequentbacteriophageinfectionsinasequence-specificmanner.HereweshowthattheStreptococcusthermophilusCRISPR1/C
4、assystemcanalsonaturallyacquirespacersfromaself-replicatingplasmidcontaininganantibiotic-resistancegene,leadingtoplasmidloss.Acquiredspacersthatmatchantibiotic-resistancegenesprovideanovelmeanstonaturallyselectbacteriathatcannotuptakeanddisseminatesuchgenes.WealsoprovideinvivoevidencethattheC
5、RISPR1/Cassystemspecificallycleavesplasmidandbacteriophagedouble-strandedDNAwithintheproto-spacer,atspecificsites.OurdatashowthattheCRISPR/CasimmunesystemisremarkablyadaptedtocleaveinvadingDNArapidlyandhasthepotentialforexploitationtogeneratesafermicrobialstrains.Clusteredregularlyinterspaced
6、shortpalindromicrepeats(CRISPR)CRISPR/Casaffectsplasmidstability1lociwerediscoveredin1987inEscherichiacoli.However,theinterestInsilicoanalysespreviouslyindicatedthatspacersmayalsobederivedinthesegeneticelementsincreasedintheearly2000s,astheywerefromS.thermophilusplasmids11.BecausetheCRISPR/Ca
7、ssystemidentified,alongwithmanyCRISPR-associated(Cas)proteins,inwasrecentlydemonstratedtointerferewithplasmidtransferinseveralprokaryotes2,3.Recently,itwasshownthattheshortspacers10Staphylococcus,weputforwardthehypothesisthattheCRISPR/(21–72b
