Comparative genomics and biological characterization of sequential XXXX isolates from persistent airways infection.

@entity1 @entity32 @entity796 @entity19 @entity1373 @entity281 @entity358 @entity1030 @entity1577
BACKGROUND: @entity796 establishes @entity1030 in @entity1577 ( @entity1577 ) @entity1 . As the disease progresses, @entity796 pathoadaptive variants are distinguished from the initially acquired strain. However, the genetic basis and the biology of host-bacteria interactions leading to a persistent lifestyle of @entity796 are not understood. As a model system to study long term and persistent @entity1577 , the @entity796 RP73, isolated 16.9  years after the onset of airways colonization from a @entity1577 @entity1 , was investigated. Comparisons with strains RP1, isolated at the onset of the colonization, and clonal RP45, isolated 7  years before RP73 were carried out to better characterize genomic evolution of @entity796 in the context of @entity1577 pathogenicity. RESULTS: Virulence assessments in disease animal model, genome sequencing and comparative genomics analysis were performed for clinical RP73, RP45, RP1 and prototype strains. In @entity19 model, RP73 showed lower lethality and a remarkable capability of long-term persistence in chronic airways infection when compared to other strains. Pathological analysis of @entity19 lungs confirmed advanced chronic @entity358 , @entity32 and mucus @entity1373 . Genomic analysis predicted twelve genomic islands in the RP73 genome, some of which distinguished RP73 from other prototype strains and corresponded to regions of genome plasticity. Further, comparative genomic analyses with sequential RP isolates showed signatures of pathoadaptive mutations in virulence factors potentially linked to the development of @entity281 in @entity1577 . CONCLUSIONS: The genome plasticity of @entity796 particularly in the RP73 strain strongly indicated that these alterations may form the genetic basis defining host-bacteria interactions leading to a persistent lifestyle in @entity1 lungs.
