TY - JOUR
T1 - Persisting uropathogenic Escherichia coli lineages show signatures of niche-specific within-host adaptation mediated by mobile genetic elements
AU - CDC Prevention Epicenters Program
AU - Thänert, Robert
AU - Choi, Joo Hee
AU - Reske, Kimberly A.
AU - Hink, Tiffany
AU - Thänert, Anna
AU - Wallace, Meghan A.
AU - Wang, Bin
AU - Seiler, Sondra
AU - Cass, Candice
AU - Bost, Margaret H.
AU - Struttmann, Emily L.
AU - Iqbal, Zainab Hassan
AU - Sax, Steven R.
AU - Fraser, Victoria J.
AU - Baker, Arthur W.
AU - Foy, Katherine R.
AU - Williams, Brett
AU - Xu, Ben
AU - Capocci-Tolomeo, Pam
AU - Lautenbach, Ebbing
AU - Burnham, Carey Ann D.
AU - Dubberke, Erik R.
AU - Kwon, Jennie H.
AU - Dantas, Gautam
N1 - Funding Information:
The authors thank Eric Keen, Drew J. Schwartz, Bejan Mahmud, Alaric D’Souza, Kimberley Sukhum, Manish Boolchandani, and Mary K. Hayden for providing scientific discussions and support. We thank the staff at the Edison Family Center for Genome Sciences and Systems Biology at Washington University School of Medicine: Bonnie Dee, Kathleen Matheny, and Keith Page for administrative support; Jessica Hoisington-Lopez and MariaLynn Crosby for managing the high-throughput sequencing core; and Eric Martin and Brian Koebbe for computational support. We thank Carrie Crook, Tony James, and Emily Reesey for providing study coordination support. This work was supported in part by awards to the authors from the U.S. Centers for Disease Control and Prevention Epicenter Prevention Program (grant U54CK000482 ; principal investigator, V.J.F.); to J.H.K. from the Longer Life Foundation (an RGA/Washington University partnership), the National Center for Advancing Translational Sciences (grants KL2TR002346 and UL1TR002345 ), and the National Institute of Allergy and Infectious Diseases (NIAID) (grant K23A1137321 ) of the National Institutes of Health (NIH); and to G.D. from NIAID (grant R01AI123394 ) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant R01HD092414 ) of NIH. R.T.’s research was funded by the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation; grant 402733540 ). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.
Funding Information:
The authors thank Eric Keen, Drew J. Schwartz, Bejan Mahmud, Alaric D'Souza, Kimberley Sukhum, Manish Boolchandani, and Mary K. Hayden for providing scientific discussions and support. We thank the staff at the Edison Family Center for Genome Sciences and Systems Biology at Washington University School of Medicine: Bonnie Dee, Kathleen Matheny, and Keith Page for administrative support; Jessica Hoisington-Lopez and MariaLynn Crosby for managing the high-throughput sequencing core; and Eric Martin and Brian Koebbe for computational support. We thank Carrie Crook, Tony James, and Emily Reesey for providing study coordination support. This work was supported in part by awards to the authors from the U.S. Centers for Disease Control and Prevention Epicenter Prevention Program (grant U54CK000482; principal investigator, V.J.F.); to J.H.K. from the Longer Life Foundation (an RGA/Washington University partnership), the National Center for Advancing Translational Sciences (grants KL2TR002346 and UL1TR002345), and the National Institute of Allergy and Infectious Diseases (NIAID) (grant K23A1137321) of the National Institutes of Health (NIH); and to G.D. from NIAID (grant R01AI123394) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant R01HD092414) of NIH. R.T.’s research was funded by the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation; grant 402733540). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. Conceptualization, J.H.K. E.R.D. C.-A.D.B. G.D. R.T. and J.C.; resources, J.H.K. E.R.D. G.D. K.A.R. S.S. C.C. M.H.B. and E.L.S.; investigation, R.T. T.H. A.T. M.A.W. B.Wang, Z.H.I. S.R.S. A.W.B. K.R.F. B.X. B.Williams, P.C.-T. E.L. and J.H.K.; data curation, K.A.R. and R.T.; bioinformatics and statistical analysis, R.T. and J.C.; writing – original draft, R.T. and J.C.; writing – review & editing, R.T. J.C. A.T. T.H. K.A.R. M.A.W. V.J.F. A.W.B. B.Williams, P.C.-T. E.L. C.-A.D.B. E.R.D. J.H.K. and G.D.; visualization, R.T. J.C. and A.T.; supervision, J.H.K. E.R.D. C.-A.D.B. and G.D.; project administration, K.A.R. and J.H.K.; funding acquisition, V.J.F. J.H.K. E.R.D. C.-A.D.B. and G.D. The authors declare no competing interests.
Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/7/13
Y1 - 2022/7/13
N2 - Large-scale genomic studies have identified within-host adaptation as a hallmark of bacterial infections. However, the impact of physiological, metabolic, and immunological differences between distinct niches on the pathoadaptation of opportunistic pathogens remains elusive. Here, we profile the within-host adaptation and evolutionary trajectories of 976 isolates representing 119 lineages of uropathogenic Escherichia coli (UPEC) sampled longitudinally from both the gastrointestinal and urinary tracts of 123 patients with urinary tract infections. We show that lineages persisting in both niches within a patient exhibit increased allelic diversity. Habitat-specific selection results in niche-specific adaptive mutations and genes, putatively mediating fitness in either environment. Within-lineage inter-habitat genomic plasticity mediated by mobile genetic elements (MGEs) provides the opportunistic pathogen with a mechanism to adapt to the physiological conditions of either habitat, and reduced MGE richness is associated with recurrence in gut-adapted UPEC lineages. Collectively, our results establish niche-specific adaptation as a driver of UPEC within-host evolution.
AB - Large-scale genomic studies have identified within-host adaptation as a hallmark of bacterial infections. However, the impact of physiological, metabolic, and immunological differences between distinct niches on the pathoadaptation of opportunistic pathogens remains elusive. Here, we profile the within-host adaptation and evolutionary trajectories of 976 isolates representing 119 lineages of uropathogenic Escherichia coli (UPEC) sampled longitudinally from both the gastrointestinal and urinary tracts of 123 patients with urinary tract infections. We show that lineages persisting in both niches within a patient exhibit increased allelic diversity. Habitat-specific selection results in niche-specific adaptive mutations and genes, putatively mediating fitness in either environment. Within-lineage inter-habitat genomic plasticity mediated by mobile genetic elements (MGEs) provides the opportunistic pathogen with a mechanism to adapt to the physiological conditions of either habitat, and reduced MGE richness is associated with recurrence in gut-adapted UPEC lineages. Collectively, our results establish niche-specific adaptation as a driver of UPEC within-host evolution.
KW - evolution
KW - genomic plasticity
KW - mobile genetic elements
KW - niche adaptation
KW - pathoadaptation
KW - uropathogenic Escherichia coli
UR - http://www.scopus.com/inward/record.url?scp=85130923534&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2022.04.008
DO - 10.1016/j.chom.2022.04.008
M3 - Article
C2 - 35545083
AN - SCOPUS:85130923534
SN - 1931-3128
VL - 30
SP - 1034-1047.e6
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 7
ER -