Molecular Evolution of the Two-Component System BvgAS Involved in Virulence Regulation in Bordetella 英文参考文献.docVIP

MolecularEvolutionoftheTwo-ComponentSystem BvgASInvolvedinVirulenceRegulationinBordetella JulienHerrou1,2,3,Anne-SophieDebrie1,2,3,EveWillery1,2,3,Genevie`veRenaud-Monge′nie4 ,Camille Locht1,2,3,FritsMooi5,Franc?oise Jacob-Dubuisson1,2,3.*,RudyAntoine1,2,3. 1InstitutNationaldelaSante′ EtdelaRechercheMe′dicale(INSERM-U629),Lille,France,2InstitutFe′de′ratifdeRecherche(IFR142),Lille,France,3InstitutPasteurdeLille, Lille,France,4Sanofi-Pasteur,Marcyl’Etoile,France,5NationalInstituteforPublicHealthandtheEnvironment,Bilthoven,TheNetherlands Abstract The whooping cough agent Bordetella pertussis is closely related to Bordetella bronchiseptica, which is responsible for chronicrespiratoryinfectionsinvariousmammalsandisoccasionallyfoundinhumans,andtoBordetellaparapertussis ,one lineage of which causes mild whooping cough in humans and the other ovine respiratory infections. All three species producesimilarsetsofvirulencefactorsthatareco-regulatedbythetwo-componentsystemBvgAS.Wecharacterizedthe molecular diversity of BvgAS in Bordetella by sequencing the two genes from a large number of diverse isolates. The responseregulatorBvgAisvirtuallyinvariant,indicatingstrongfunctionalconstraints.Incontrast,themulti-domainsensor kinaseBvgShasevolvedintotwodifferenttypes.ThepertussistypeisfoundinB.pertussisandinalineageofessentially human-associatedB.bronchiseptica,whilethebronchisepticatypeisassociatedwiththemajorityofB.bronchisepticaand both ovine and human B. parapertussis. BvgS is monomorphic in B. pertussis, suggesting optimal adaptation or a recent population bottleneck. The degree of diversity of the bronchiseptica type BvgS is markedly different between domains, indicating distinct evolutionary pressures. Thus, absolute conservation of the putative solute-binding cavities of the two periplasmic Venus Fly Trap (VFT) domains suggests that common signals are perceived in all three species, while the externalsurfacesofthesedomainsvarymoreextensively.Co-evolutionofthesurfacesoft