Evolutionary highways to persistent bacterial infection

TY - JOUR

T1 - Evolutionary highways to persistent bacterial infection

AU - Bartell, Jennifer A

AU - Sommer, Lea M

AU - Haagensen, Janus A J

AU - Loch, Anne

AU - Espinosa, Rocio

AU - Molin, Søren

AU - Johansen, Helle Krogh

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Persistent infections require bacteria to evolve from their naïve colonization state by optimizing fitness in the host via simultaneous adaptation of multiple traits, which can obscure evolutionary trends and complicate infection management. Accordingly, here we screen 8 infection-relevant phenotypes of 443 longitudinal Pseudomonas aeruginosa isolates from 39 young cystic fibrosis patients over 10 years. Using statistical modeling, we map evolutionary trajectories and identify trait correlations accounting for patient-specific influences. By integrating previous genetic analyses of 474 isolates, we provide a window into early adaptation to the host, finding: (1) a 2-3 year timeline of rapid adaptation after colonization, (2) variant "naïve" and "adapted" states reflecting discordance between phenotypic and genetic adaptation, (3) adaptive trajectories leading to persistent infection via three distinct evolutionary modes, and (4) new associations between phenotypes and pathoadaptive mutations. Ultimately, we effectively deconvolute complex trait adaptation, offering a framework for evolutionary studies and precision medicine in clinical microbiology.

AB - Persistent infections require bacteria to evolve from their naïve colonization state by optimizing fitness in the host via simultaneous adaptation of multiple traits, which can obscure evolutionary trends and complicate infection management. Accordingly, here we screen 8 infection-relevant phenotypes of 443 longitudinal Pseudomonas aeruginosa isolates from 39 young cystic fibrosis patients over 10 years. Using statistical modeling, we map evolutionary trajectories and identify trait correlations accounting for patient-specific influences. By integrating previous genetic analyses of 474 isolates, we provide a window into early adaptation to the host, finding: (1) a 2-3 year timeline of rapid adaptation after colonization, (2) variant "naïve" and "adapted" states reflecting discordance between phenotypic and genetic adaptation, (3) adaptive trajectories leading to persistent infection via three distinct evolutionary modes, and (4) new associations between phenotypes and pathoadaptive mutations. Ultimately, we effectively deconvolute complex trait adaptation, offering a framework for evolutionary studies and precision medicine in clinical microbiology.

KW - Biological Evolution

KW - Cystic Fibrosis/microbiology

KW - Humans

KW - Models, Statistical

KW - Mutation/genetics

KW - Pseudomonas Infections/genetics

KW - Pseudomonas aeruginosa/pathogenicity

U2 - 10.1038/s41467-019-08504-7

DO - 10.1038/s41467-019-08504-7

M3 - Journal article

C2 - 30733448

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 629

ER -