Format

Send to

Choose Destination
Nat Microbiol. 2019 Jan;4(1):112-123. doi: 10.1038/s41564-018-0292-6. Epub 2018 Nov 26.

Prediction of the intestinal resistome by a three-dimensional structure-based method.

Author information

1
MGP MetaGénoPolis, INRA, Université Paris-Saclay, Jouy en Josas, France. etienne.ruppe@inserm.fr.
2
IAME, UMR 1137, INSERM, Paris Diderot University, Sorbonne Paris Cité, Paris, France. etienne.ruppe@inserm.fr.
3
MGP MetaGénoPolis, INRA, Université Paris-Saclay, Jouy en Josas, France.
4
Institut Pasteur - Bioinformatics and Biostatistics Hub - C3BI, USR 3756 IP CNRS, Paris, France.
5
Institut Pasteur - Biomics - CITECH, Paris, France.
6
Danone Nutricia Research, Palaiseau, France.
7
Centro Nacional de Biotecnología, CSIC, Madrid, Spain.
8
Servicio de Microbiología Instituto, Ramón y Cajal de Investigación Sanitaria, Madrid, Spain.
9
CIBER en Epidemiología y Salud Pública, Madrid, Spain.
10
Unidad de Resistencia a Antibióticos y Virulencia Bacteriana, Madrid, Spain.
11
Unit for Cystic Fibrosis, Ramon y Cajal University Hospital, Madrid, Spain.
12
Internal Medicine Department, Beaujon Hospital, AP-HP, Clichy, France.
13
IAME, UMR 1137, INSERM, Paris Diderot University, Sorbonne Paris Cité, Paris, France.
14
Bacteriology Laboratory, Bichat-Claude Bernard Hospital, AP-HP, Paris, France.
15
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.
16
Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham, UK.
17
INSERM UMR_S 1134, Paris Diderot University, Sorbonne Paris Cité, Université de la Réunion, Université des Antilles, INTS, GR-Ex, Paris, France.
18
Centre of Host Microbiome Interactions, King's College, London, UK.

Abstract

The intestinal microbiota is considered to be a major reservoir of antibiotic resistance determinants (ARDs) that could potentially be transferred to bacterial pathogens via mobile genetic elements. Yet, this assumption is poorly supported by empirical evidence due to the distant homologies between known ARDs (mostly from culturable bacteria) and ARDs from the intestinal microbiota. Consequently, an accurate census of intestinal ARDs (that is, the intestinal resistome) has not yet been fully determined. For this purpose, we developed and validated an annotation method (called pairwise comparative modelling) on the basis of a three-dimensional structure (homology comparative modelling), leading to the prediction of 6,095 ARDs in a catalogue of 3.9 million proteins from the human intestinal microbiota. We found that the majority of predicted ARDs (pdARDs) were distantly related to known ARDs (mean amino acid identity 29.8%) and found little evidence supporting their transfer between species. According to the composition of their resistome, we were able to cluster subjects from the MetaHIT cohort (n = 663) into six resistotypes that were connected to the previously described enterotypes. Finally, we found that the relative abundance of pdARDs was positively associated with gene richness, but not when subjects were exposed to antibiotics. Altogether, our results indicate that the majority of intestinal microbiota ARDs can be considered intrinsic to the dominant commensal microbiota and that these genes are rarely shared with bacterial pathogens.

PMID:
30478291
DOI:
10.1038/s41564-018-0292-6

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center