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

Bakkeren, Erik and Herter, Joana Anuschka and Huisman, Jana Sanne and Steiger, Yves and Gül, Ersin and Newson, Joshua Patrick Mark and Brachmann, Alexander Oliver and Piel, Jörn and Regoes, Roland and Bonhoeffer, Sebastian and Diard, Médéric and Hardt, Wolf-Dietrich. (2021) Pathogen invasion-dependent tissue reservoirs and plasmid-encoded antibiotic degradation boost plasmid spread in the gut. eLife, 10. e69744.

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Pathogen Evolution (Diard)
UniBasel Contributors:Diard, Médéric
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:eLife Sciences Publications
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Mar 2022 09:01
Deposited On:08 Mar 2022 09:01

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