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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

Journal article
Authors H. Gumpert
J. Z. Kubicek-Sutherland
A. Porse
Nahid Karami
C. Munck
M. Linkevicius
Ingegerd Adlerberth
Agnes E Wold
D. I. Andersson
M. O. A. Sommer
Published in Frontiers in Microbiology
Volume 8
ISSN 1664-302X
Publication year 2017
Published at Institute of Biomedicine, Department of Infectious Medicine
Language en
Links dx.doi.org/10.3389/fmicb.2017.01852
Keywords Escherichia coli, horizontal gene transfer, infant gut, genome dynamics, plasmid transfer, in vivo, escherichia-coli, ampicillin resistance, klebsiella-pneumoniae, mouse, intestine, gene-transfer, vivo transfer, sequence, colonization, virulence, elements, Microbiology, CONNELL M A, 1991, Microbial Ecology in Health and Disease, V4, P343
Subject categories Microbiology in the medical area

Abstract

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.

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