Cable Pili and the Associated 22 Kda Adhesin Contribute to Burkholderia Cenocepacia Persistence In Vivo 英文参考文献.docVIP

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Cable Pili and the Associated 22 Kda Adhesin Contribute to Burkholderia Cenocepacia Persistence In Vivo 英文参考文献.doc

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Cable Pili and the Associated 22 Kda Adhesin Contribute to Burkholderia Cenocepacia Persistence In Vivo 英文参考文献

CablePiliandtheAssociated22KdaAdhesinContribute toBurkholderiaCenocepaciaPersistenceInVivo JoannaB.Goldberg1,ShyamalaGanesan2,AdamT.Comstock2,YingZhao2,UmaS.Sajjan2* 1Department ofMicrobiology,University ofVirginia HealthSystem, Charlottesville,Virginia, United StatesofAmerica, 2Department ofPediatrics andCommunicable Diseases,UniversityofMichigan,AnnArbor,Michigan,UnitedStatesofAmerica Abstract Background:InfectionbyBurkholderiacenocepaciaincysticfibrosis(CF)patientsisassociatedwithpoorclinicalprognosis. Previously,wedemonstratedthatoneofthehighlytransmissiblestrains,BC7,expressescablepiliandtheassociated22kDa adhesin,bothofwhichcontributetoBC7bindingtoairwayepithelialcells.However,thecontributionofthesefactorsto induceinflammationandbacterialpersistenceinvivoisnotknown. Methodology/PrincipalFindings:Wild-typeBC7stimulatedhigherIL-8responsesthantheBC7cblandBC7adhAmutants in both CF and normal bronchial epithelial cells. To determine the role of cable pili and the associated adhesin, we characterizedamousemodelofB.cenocepacia,whereBC7aresuspendedinPseudomonasaeruginosaalginate.C57BL/6 mice were infected intratracheally withwild-type BC7 suspended in either alginateor PBS andwere monitored for lung bacterialloadandinflammation.MiceinfectedwithBC7suspendedinPBScompletelyclearedthebacteriaby3daysand resolvedtheinflammation.Incontrast,miceinfectedwithBC7suspendedinalginateshowedpersistenceofbacteriaand moderatelunginflammationupto5dayspost-infection.Usingthismodel,miceinfectedwiththeBC7cblandBC7adhA mutants showed lower bacterial loads and mild inflammation compared to mice infected with wild-type BC7. ComplementationoftheBC7cblSmutationintransrestoredthecapacityofthisstraintopersistinvivo.Immunolocalization ofbacteriarevealedwild-typeBC7inbothairwaylumenandalveoli,whiletheBC7cblandBC7adhAmutantswerefound mainlyinairwaylumenandperibronchiolarregion. ConclusionsandSignificance:B.cenocepaciasuspendedinalginatecanbeusedtodeterminethecapacityofbacteriato persistandcau