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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/69744 |
| _version_ | 1811200799377719296 |
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| author | Erik Bakkeren Joana Anuschka Herter Jana Sanne Huisman Yves Steiger Ersin Gül Joshua Patrick Mark Newson Alexander Oliver Brachmann Jörn Piel Roland Regoes Sebastian Bonhoeffer Médéric Diard Wolf-Dietrich Hardt |
| author_facet | Erik Bakkeren Joana Anuschka Herter Jana Sanne Huisman Yves Steiger Ersin Gül Joshua Patrick Mark Newson Alexander Oliver Brachmann Jörn Piel Roland Regoes Sebastian Bonhoeffer Médéric Diard Wolf-Dietrich Hardt |
| author_sort | Erik Bakkeren |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T02:09:47Z |
| format | Article |
| id | doaj.art-253fa6dc03ec4bdda054770ebfbfe7c4 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:09:47Z |
| publishDate | 2021-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-253fa6dc03ec4bdda054770ebfbfe7c42022-12-22T03:52:26ZengeLife Sciences Publications LtdeLife2050-084X2021-12-011010.7554/eLife.69744Pathogen invasion-dependent tissue reservoirs and plasmid-encoded antibiotic degradation boost plasmid spread in the gutErik Bakkeren0https://orcid.org/0000-0001-7970-7890Joana Anuschka Herter1Jana Sanne Huisman2https://orcid.org/0000-0002-1782-8109Yves Steiger3Ersin Gül4https://orcid.org/0000-0003-2873-8034Joshua Patrick Mark Newson5https://orcid.org/0000-0003-2091-7943Alexander Oliver Brachmann6Jörn Piel7Roland Regoes8https://orcid.org/0000-0001-8319-5293Sebastian Bonhoeffer9https://orcid.org/0000-0001-8052-3925Médéric Diard10https://orcid.org/0000-0003-0851-4391Wolf-Dietrich Hardt11https://orcid.org/0000-0002-9892-6420Institute of Microbiology, Department of Biology, ETH Zurich, Zurich, SwitzerlandInstitute of Microbiology, Department of Biology, ETH Zurich, Zurich, SwitzerlandSwiss Institute of Bioinformatics, Lausanne, Switzerland; Institute of Integrative Biology, Department of Environmental Systems Science, ETH Zurich, Zurich, SwitzerlandInstitute of Microbiology, Department of Biology, ETH Zurich, Zurich, SwitzerlandInstitute of Microbiology, Department of Biology, ETH Zurich, Zurich, SwitzerlandInstitute of Microbiology, Department of Biology, ETH Zurich, Zurich, SwitzerlandInstitute of Microbiology, Department of Biology, ETH Zurich, Zurich, SwitzerlandInstitute of Microbiology, Department of Biology, ETH Zurich, Zurich, SwitzerlandInstitute of Integrative Biology, Department of Environmental Systems Science, ETH Zurich, Zurich, SwitzerlandInstitute of Integrative Biology, Department of Environmental Systems Science, ETH Zurich, Zurich, SwitzerlandBotnar Research Centre for Child Health, Basel, Switzerland; Biozentrum, University of Basel, Basel, SwitzerlandInstitute of Microbiology, Department of Biology, ETH Zurich, Zurich, SwitzerlandMany 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.https://elifesciences.org/articles/69744plasmidsSalmonellaantibiotic resistancetissue reservoirspersistence |
| spellingShingle | Erik Bakkeren Joana Anuschka Herter Jana Sanne Huisman Yves Steiger Ersin Gül Joshua Patrick Mark Newson Alexander Oliver Brachmann Jörn Piel Roland Regoes Sebastian Bonhoeffer Médéric Diard Wolf-Dietrich Hardt Pathogen invasion-dependent tissue reservoirs and plasmid-encoded antibiotic degradation boost plasmid spread in the gut eLife plasmids Salmonella antibiotic resistance tissue reservoirs persistence |
| 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 | plasmids Salmonella antibiotic resistance tissue reservoirs persistence |
| url | https://elifesciences.org/articles/69744 |
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