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Genome-Wide Screening for Enteric Colonization Factors in Carbapenem-Resistant ST258 Klebsiella pneumoniae

A diverse, antibiotic-naive microbiota prevents highly antibiotic-resistant microbes, including carbapenem-resistant Klebsiella pneumoniae (CR-Kp), from achieving dense colonization of the intestinal lumen. Antibiotic-mediated destruction of the microbiota leads to expansion of CR-Kp in the gut, mar...

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Autores principales: Jung, Hea-Jin, Littmann, Eric R., Seok, Ruth, Leiner, Ingrid M., Taur, Ying, Peled, Jonathan, van den Brink, Marcel, Ling, Lilan, Chen, Liang, Kreiswirth, Barry N., Goodman, Andrew L., Pamer, Eric G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6414703/
https://www.ncbi.nlm.nih.gov/pubmed/30862751
http://dx.doi.org/10.1128/mBio.02663-18
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author Jung, Hea-Jin
Littmann, Eric R.
Seok, Ruth
Leiner, Ingrid M.
Taur, Ying
Peled, Jonathan
van den Brink, Marcel
Ling, Lilan
Chen, Liang
Kreiswirth, Barry N.
Goodman, Andrew L.
Pamer, Eric G.
author_facet Jung, Hea-Jin
Littmann, Eric R.
Seok, Ruth
Leiner, Ingrid M.
Taur, Ying
Peled, Jonathan
van den Brink, Marcel
Ling, Lilan
Chen, Liang
Kreiswirth, Barry N.
Goodman, Andrew L.
Pamer, Eric G.
author_sort Jung, Hea-Jin
collection PubMed
description A diverse, antibiotic-naive microbiota prevents highly antibiotic-resistant microbes, including carbapenem-resistant Klebsiella pneumoniae (CR-Kp), from achieving dense colonization of the intestinal lumen. Antibiotic-mediated destruction of the microbiota leads to expansion of CR-Kp in the gut, markedly increasing the risk of bacteremia in vulnerable patients. While preventing dense colonization represents a rational approach to reduce intra- and interpatient dissemination of CR-Kp, little is known about pathogen-associated factors that enable dense growth and persistence in the intestinal lumen. To identify genetic factors essential for dense colonization of the gut by CR-Kp, we constructed a highly saturated transposon mutant library with >150,000 unique mutations in an ST258 strain of CR-Kp and screened for in vitro growth and in vivo intestinal colonization in antibiotic-treated mice. Stochastic and partially reversible fluctuations in the representation of different mutations during dense colonization revealed the dynamic nature of intestinal microbial populations. We identified genes that are crucial for early and late stages of dense gut colonization and confirmed their role by testing isogenic mutants in in vivo competition assays with wild-type CR-Kp. Screening of the transposon library also identified mutations that enhanced in vivo CR-Kp growth. These newly identified colonization factors may provide novel therapeutic opportunities to reduce intestinal colonization by CR-Kp.
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spelling pubmed-64147032019-03-22 Genome-Wide Screening for Enteric Colonization Factors in Carbapenem-Resistant ST258 Klebsiella pneumoniae Jung, Hea-Jin Littmann, Eric R. Seok, Ruth Leiner, Ingrid M. Taur, Ying Peled, Jonathan van den Brink, Marcel Ling, Lilan Chen, Liang Kreiswirth, Barry N. Goodman, Andrew L. Pamer, Eric G. mBio Research Article A diverse, antibiotic-naive microbiota prevents highly antibiotic-resistant microbes, including carbapenem-resistant Klebsiella pneumoniae (CR-Kp), from achieving dense colonization of the intestinal lumen. Antibiotic-mediated destruction of the microbiota leads to expansion of CR-Kp in the gut, markedly increasing the risk of bacteremia in vulnerable patients. While preventing dense colonization represents a rational approach to reduce intra- and interpatient dissemination of CR-Kp, little is known about pathogen-associated factors that enable dense growth and persistence in the intestinal lumen. To identify genetic factors essential for dense colonization of the gut by CR-Kp, we constructed a highly saturated transposon mutant library with >150,000 unique mutations in an ST258 strain of CR-Kp and screened for in vitro growth and in vivo intestinal colonization in antibiotic-treated mice. Stochastic and partially reversible fluctuations in the representation of different mutations during dense colonization revealed the dynamic nature of intestinal microbial populations. We identified genes that are crucial for early and late stages of dense gut colonization and confirmed their role by testing isogenic mutants in in vivo competition assays with wild-type CR-Kp. Screening of the transposon library also identified mutations that enhanced in vivo CR-Kp growth. These newly identified colonization factors may provide novel therapeutic opportunities to reduce intestinal colonization by CR-Kp. American Society for Microbiology 2019-03-12 /pmc/articles/PMC6414703/ /pubmed/30862751 http://dx.doi.org/10.1128/mBio.02663-18 Text en Copyright © 2019 Jung et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Jung, Hea-Jin
Littmann, Eric R.
Seok, Ruth
Leiner, Ingrid M.
Taur, Ying
Peled, Jonathan
van den Brink, Marcel
Ling, Lilan
Chen, Liang
Kreiswirth, Barry N.
Goodman, Andrew L.
Pamer, Eric G.
Genome-Wide Screening for Enteric Colonization Factors in Carbapenem-Resistant ST258 Klebsiella pneumoniae
title Genome-Wide Screening for Enteric Colonization Factors in Carbapenem-Resistant ST258 Klebsiella pneumoniae
title_full Genome-Wide Screening for Enteric Colonization Factors in Carbapenem-Resistant ST258 Klebsiella pneumoniae
title_fullStr Genome-Wide Screening for Enteric Colonization Factors in Carbapenem-Resistant ST258 Klebsiella pneumoniae
title_full_unstemmed Genome-Wide Screening for Enteric Colonization Factors in Carbapenem-Resistant ST258 Klebsiella pneumoniae
title_short Genome-Wide Screening for Enteric Colonization Factors in Carbapenem-Resistant ST258 Klebsiella pneumoniae
title_sort genome-wide screening for enteric colonization factors in carbapenem-resistant st258 klebsiella pneumoniae
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6414703/
https://www.ncbi.nlm.nih.gov/pubmed/30862751
http://dx.doi.org/10.1128/mBio.02663-18
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