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Pathogen invasion-dependent tissue reservoirs and plasmid-encoded antibiotic degradation boost plasmid spread in the gut

Many plasmids encode antibiotic resistance genes. Through conjugation, plasmids can be rapidly disseminated. Previous work identified gut luminal donor/recipient blooms and tissue-lodged plasmid-bearing persister cells of the enteric pathogen Salmonella enterica serovar Typhimurium (S.Tm) that survi...

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Autores principales: Bakkeren, Erik, Herter, Joana Anuschka, Huisman, Jana Sanne, Steiger, Yves, Gül, Ersin, Newson, Joshua Patrick Mark, Brachmann, Alexander Oliver, Piel, Jörn, Regoes, Roland, Bonhoeffer, Sebastian, Diard, Médéric, Hardt, Wolf-Dietrich
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651294/
https://www.ncbi.nlm.nih.gov/pubmed/34872631
http://dx.doi.org/10.7554/eLife.69744
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author Bakkeren, Erik
Herter, Joana Anuschka
Huisman, Jana Sanne
Steiger, Yves
Gül, Ersin
Newson, Joshua Patrick Mark
Brachmann, Alexander Oliver
Piel, Jörn
Regoes, Roland
Bonhoeffer, Sebastian
Diard, Médéric
Hardt, Wolf-Dietrich
author_facet Bakkeren, Erik
Herter, Joana Anuschka
Huisman, Jana Sanne
Steiger, Yves
Gül, Ersin
Newson, Joshua Patrick Mark
Brachmann, Alexander Oliver
Piel, Jörn
Regoes, Roland
Bonhoeffer, Sebastian
Diard, Médéric
Hardt, Wolf-Dietrich
author_sort Bakkeren, Erik
collection PubMed
description Many plasmids encode antibiotic resistance genes. Through conjugation, plasmids can be rapidly disseminated. Previous work identified gut luminal donor/recipient blooms and tissue-lodged plasmid-bearing persister cells of the enteric pathogen Salmonella enterica serovar Typhimurium (S.Tm) that survive antibiotic therapy in host tissues, as factors promoting plasmid dissemination among Enterobacteriaceae. However, the buildup of tissue reservoirs and their contribution to plasmid spread await experimental demonstration. Here, we asked if re-seeding-plasmid acquisition-invasion cycles by S.Tm could serve to diversify tissue-lodged plasmid reservoirs, and thereby promote plasmid spread. Starting with intraperitoneal mouse infections, we demonstrate that S.Tm cells re-seeding the gut lumen initiate clonal expansion. Extended spectrum beta-lactamase (ESBL) plasmid-encoded gut luminal antibiotic degradation by donors can foster recipient survival under beta-lactam antibiotic treatment, enhancing transconjugant formation upon re-seeding. S.Tm transconjugants can subsequently re-enter host tissues introducing the new plasmid into the tissue-lodged reservoir. Population dynamics analyses pinpoint recipient migration into the gut lumen as rate-limiting for plasmid transfer dynamics in our model. Priority effects may be a limiting factor for reservoir formation in host tissues. Overall, our proof-of-principle data indicates that luminal antibiotic degradation and shuttling between the gut lumen and tissue-resident reservoirs can promote the accumulation and spread of plasmids within a host over time.
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spelling pubmed-86512942021-12-09 Pathogen invasion-dependent tissue reservoirs and plasmid-encoded antibiotic degradation boost plasmid spread in the gut Bakkeren, Erik Herter, Joana Anuschka Huisman, Jana Sanne Steiger, Yves Gül, Ersin Newson, Joshua Patrick Mark Brachmann, Alexander Oliver Piel, Jörn Regoes, Roland Bonhoeffer, Sebastian Diard, Médéric Hardt, Wolf-Dietrich eLife Evolutionary Biology Many plasmids encode antibiotic resistance genes. Through conjugation, plasmids can be rapidly disseminated. Previous work identified gut luminal donor/recipient blooms and tissue-lodged plasmid-bearing persister cells of the enteric pathogen Salmonella enterica serovar Typhimurium (S.Tm) that survive antibiotic therapy in host tissues, as factors promoting plasmid dissemination among Enterobacteriaceae. However, the buildup of tissue reservoirs and their contribution to plasmid spread await experimental demonstration. Here, we asked if re-seeding-plasmid acquisition-invasion cycles by S.Tm could serve to diversify tissue-lodged plasmid reservoirs, and thereby promote plasmid spread. Starting with intraperitoneal mouse infections, we demonstrate that S.Tm cells re-seeding the gut lumen initiate clonal expansion. Extended spectrum beta-lactamase (ESBL) plasmid-encoded gut luminal antibiotic degradation by donors can foster recipient survival under beta-lactam antibiotic treatment, enhancing transconjugant formation upon re-seeding. S.Tm transconjugants can subsequently re-enter host tissues introducing the new plasmid into the tissue-lodged reservoir. Population dynamics analyses pinpoint recipient migration into the gut lumen as rate-limiting for plasmid transfer dynamics in our model. Priority effects may be a limiting factor for reservoir formation in host tissues. Overall, our proof-of-principle data indicates that luminal antibiotic degradation and shuttling between the gut lumen and tissue-resident reservoirs can promote the accumulation and spread of plasmids within a host over time. eLife Sciences Publications, Ltd 2021-12-07 /pmc/articles/PMC8651294/ /pubmed/34872631 http://dx.doi.org/10.7554/eLife.69744 Text en © 2021, Bakkeren et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Evolutionary Biology
Bakkeren, Erik
Herter, Joana Anuschka
Huisman, Jana Sanne
Steiger, Yves
Gül, Ersin
Newson, Joshua Patrick Mark
Brachmann, Alexander Oliver
Piel, Jörn
Regoes, Roland
Bonhoeffer, Sebastian
Diard, Médéric
Hardt, Wolf-Dietrich
Pathogen invasion-dependent tissue reservoirs and plasmid-encoded antibiotic degradation boost plasmid spread in the gut
title Pathogen invasion-dependent tissue reservoirs and plasmid-encoded antibiotic degradation boost plasmid spread in the gut
title_full Pathogen invasion-dependent tissue reservoirs and plasmid-encoded antibiotic degradation boost plasmid spread in the gut
title_fullStr Pathogen invasion-dependent tissue reservoirs and plasmid-encoded antibiotic degradation boost plasmid spread in the gut
title_full_unstemmed Pathogen invasion-dependent tissue reservoirs and plasmid-encoded antibiotic degradation boost plasmid spread in the gut
title_short Pathogen invasion-dependent tissue reservoirs and plasmid-encoded antibiotic degradation boost plasmid spread in the gut
title_sort pathogen invasion-dependent tissue reservoirs and plasmid-encoded antibiotic degradation boost plasmid spread in the gut
topic Evolutionary Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651294/
https://www.ncbi.nlm.nih.gov/pubmed/34872631
http://dx.doi.org/10.7554/eLife.69744
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