?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F8093%2F&rft.title=MOLECULAR+CHARACTERIZATION+OF+IS1301+IN+AN+EMERGENT+CLONE+OF+SEROGROUP+C+NEISSERIA+MENINGITIDIS&rft.creator=Conley%2C+Ashley+Marie&rft.description=Neisseria+meningitidis+is+a+leading+cause+of+invasive+meningococcal+disease+and+humans+are+the+only+known+host.+The+administration+of+meningococcal+vaccines+has+reduced+the+number+of+meningococcal+cases+and+carriage+rates+in+humans.+Current+vaccine+strategies+target+important+immunological+determinants.+Insertion+sequence+1301+(IS1301)+has+been+shown+to+facilitate+evasion+of+the+host+immune+response+by+disrupting+antigen+expression.+The+public+health+importance+of+this+study+is+in+the+design+of+future+vaccines+against+N.+meningitidis+and+in+understanding+the+emergence+of+new+clones.+In+the+1990s+there+was+an+increase+in+serogroup+C+meningococcal+disease+in+Maryland+that+was+associated+with+antigenic+shift+at+the+fetA+gene.+The+isolates+were+characterized+as+either+an+early+clone+or+late+clone+based+on+the+outer+membrane+protein+sequence+profiles.+The+2%3AP1.5%2C2%3AF.1-30+sequence+profile+is+classified+as+an+early+clone+while+the+2%3AP1.5%2C2%3AF.3-6+sequence+profile+is+classified+as+a+late+clone.+Previous+studies+determined+that+the+late+clone+contained+IS1301%2C+while+the+early+clone+did+not.+The+goal+of+this+present+study+is+to+characterize+the+IS1301+insertion+sites+in+the+late+clone+to+determine+if+this+genetic+element+contributed+to+clonal+emergence.+Early+and+late+clone+isolates+were+characterized+by+DNA+sequence+analysis+of+the+housekeeping+gene%2C+fumC.+A+single+nucleotide+polymorphism+characteristic+of+the+hypervirulent+ET-15+clone+was+identified+in+the+late+clone+isolates.+Southern+blot+analysis+using+an+IS1301+probe+revealed+a+heterogeneous+population+with+multiple+insertion+sites%2C+ranging+from+five+to+ten+insertions%2C+within+the+serogroup+C+late+clone+genomes.+Of+note+was+a+high+molecular+weight+triplet+banding+pattern+common+to+the+majority+of+isolates.+Several+different+IS1301+specific%2C+PCR-based+strategies+were+performed+in+an+attempt+to+clone+the+IS1301+elements+corresponding+to+the+bands+of+the+IS1301+triplet.+In+addition%2C+whole+genome+sequence+analysis+was+performed+on+one+of+the+late+clone+isolates.+Initial+whole+genome+analysis+demonstrates+IS1301+integration+within+an+opacity-associated+protein+(Opa)%2C+which+promotes+adherence+to+host+cells.+Further+investigations+are+necessary+to+determine+the+effect+of+IS1301+insertion+on+antigenic+variation.&rft.date=2008-09-28&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F8093%2F1%2FConley_Ashley_ETD2008.pdf&rft.identifier=++Conley%2C+Ashley+Marie++(2008)+MOLECULAR+CHARACTERIZATION+OF+IS1301+IN+AN+EMERGENT+CLONE+OF+SEROGROUP+C+NEISSERIA+MENINGITIDIS.++Master's+Thesis%2C+University+of+Pittsburgh.++++(Unpublished)++