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Salmonella persisters promote the spread of antibiotic resistance plasmids in the gut
Swiss Fed Inst Technol, Dept Biol, Inst Microbiol, Zurich, Switzerland.
Swiss Fed Inst Technol, Inst Integrat Biol, Dept Environm Syst Sci, Zurich, Switzerland;Swiss Inst Bioinformat, Lausanne, Switzerland.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Swiss Fed Inst Technol, Dept Biol, Inst Microbiol, Zurich, Switzerland;Uppsala Univ, Sci Life Lab, Dept Med Biochem & Microbiol, Uppsala, Sweden.
Swiss Fed Inst Technol, Dept Biol, Inst Microbiol, Zurich, Switzerland.
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2019 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 573, no 7773, p. 276-280Article in journal (Refereed) Published
Abstract [en]

The emergence of antibiotic-resistant bacteria through mutations or the acquisition of genetic material such as resistance plasmids represents a major public health issue(1,2). Persisters are subpopulations of bacteria that survive antibiotics by reversibly adapting their physiology(3-10), and can promote the emergence of antibiotic-resistant mutants(11). We investigated whether persisters can also promote the spread of resistance plasmids. In contrast to mutations, the transfer of resistance plasmids requires the co-occurrence of both a donor and a recipient bacterial strain. For our experiments, we chose the facultative intracellular entero-pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) and Escherichia coli, a common member of the microbiota(12). S. Typhimurium forms persisters that survive antibiotic therapy in several host tissues. Here we show that tissue-associated S. Typhimurium persisters represent long-lived reservoirs of plasmid donors or recipients. The formation of reservoirs of S. Typhimurium persisters requires Salmonella pathogenicity island (SPI)-1 and/or SPI-2 in gut-associated tissues, or SPI-2 at systemic sites. The re-seeding of these persister bacteria into the gut lumen enables the co-occurrence of donors with gut-resident recipients, and thereby favours plasmid transfer between various strains of Enterobacteriaceae. We observe up to 99% transconjugants within two to three days of re-seeding. Mathematical modelling shows that rare re-seeding events may suffice for a high frequency of conjugation. Vaccination reduces the formation of reservoirs of persisters after oral infection with S. Typhimurium, as well as subsequent plasmid transfer. We conclude that-even without selection for plasmid-encoded resistance genes-small reservoirs of pathogen persisters can foster the spread of promiscuous resistance plasmids in the gut.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2019. Vol. 573, no 7773, p. 276-280
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Microbiology in the medical area
Identifiers
URN: urn:nbn:se:uu:diva-395313DOI: 10.1038/s41586-019-1521-8ISI: 000485415400058PubMedID: 31485077OAI: oai:DiVA.org:uu-395313DiVA, id: diva2:1362219
Funder
EU, FP7, Seventh Framework Programme, 407240-167121Swedish Research Council, 2015-00635Swedish Research Council, 2018-02223Available from: 2019-10-18 Created: 2019-10-18 Last updated: 2019-10-18Bibliographically approved

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Fattinger, Stefan A.Sellin, Mikael E.

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