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Transfer and Persistence of a Multi-Drug Resistance Plasmid in situ of the Infant Gut Microbiotain the Absence of Antibiotic Treatment
Tech Univ Denmark, Dept Syst Biol, Lyngby, Denmark.;Univ Copenhagen, Hvidovre Hosp, Dept Clin Microbiol, Hvidovre, Denmark..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Tech Univ Denmark, Novo Nordisk Fdn, Ctr Biosustainabil, Lyngby, Denmark..
Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Infect Dis, Gothenburg, Sweden..
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2017 (English)In: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 8, article id 1852Article in journal (Refereed) Published
Abstract [en]

The microbial ecosystem residing in the human gut is believed to play an important role in horizontal exchange of virulence and antibiotic resistance genes that threatens human health. While the diversity of gut-microorganisms and their genetic content has been studied extensively, high-resolution insight into the plasticity, and selective forces shaping individual genomes is scarce. In a longitudinal study, we followed the dynamics of co-existing Escherichia coli lineages in an infant not receiving antibiotics. Using whole genome sequencing, we observed large genomic deletions, bacteriophage infections, as well as the loss and acquisition of plasmids in these lineages during their colonization of the human gut. In particular, we captured the exchange of multidrug resistance genes, and identified a clinically relevant conjugative plasmid mediating the transfer. This resistant transconjugant lineage was maintained for months, demonstrating that antibiotic resistance genes can disseminate and persist in the gut microbiome; even in absence of antibiotic selection. Furthermore, through in vivo competition assays, we suggest that the resistant transconjugant can persist through a fitness advantage in the mouse gut in spite of a fitness cost in vitro. Our findings highlight the dynamic nature of the human gut microbiota and provide the first genomic description of antibiotic resistance gene transfer between bacteria in the unperturbed human gut. These results exemplify that conjugative plasmids, harboring resistance determinants, can transfer and persists in the gut in the absence of antibiotic treatment.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA , 2017. Vol. 8, article id 1852
Keyword [en]
Escherichia coli, horizontal gene transfer, infant gut, genome dynamics, plasmid transfer, in vivo fitness, mouse models, antibiotic resistance
National Category
Microbiology
Identifiers
URN: urn:nbn:se:uu:diva-336475DOI: 10.3389/fmicb.2017.01852ISI: 000411748800003PubMedID: 29018426OAI: oai:DiVA.org:uu-336475DiVA, id: diva2:1168407
Available from: 2017-12-20 Created: 2017-12-20 Last updated: 2017-12-20Bibliographically approved

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Linkevicius, MariusAndersson, Dan I.
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