Journal Article

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

Pons, Nicolas, Hospital Universitario Ramón y Cajal, Blottiere, Herve, H., Fantin, Bruno, MetaGenoPolis, Coque, Teresa, de Lastours, Victoire, Weiszer, Kevin, Haimet, Florence, Lanza, Val, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Dore, Joel, Biomics, Service de Médecine Interne, Willems, Rob, Ruppé, Etienne, Andremont, Antoine, Léjard, Véronique, de Brevern, Alexandre, Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, van Schaik, Willem, ANR-11-DPBS-0001, MGP,MetaGenoPolis, Martínez, Jose Luís, Wieder, Ingrid, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Kennedy, Sean, Maziers, Nicolas, Amor, Nawal, Hernando-Amado, Sara, Goulenok, Tiphaine, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon, Zhang, Xinglin, Ehrlich, S. Dusko, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Baquero, Fernando, Letur, Aline, Cuesta, Trinidad, Levenez, Florence, AP-HP - Hôpital Bichat - Claude Bernard, Centro Nac

2019

Overview

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.

• Publisher: Nature Publishing Group,CCSD,Nature Publishing Group UK
• Subject: 45/23 / 631/114 / 631/326/22/1434 / 631/326/2565/2134 / Amino acid composition / Amino acids / Anti-Bacterial Agents - pharmacology / Antibiotic resistance / Antibiotics / Bacteria - classification / Bacteria - drug effects / Bacteria - genetics / Bacterial Proteins - chemistry / Bacterial Proteins - genetics / beta-Lactamases - chemistry / beta-Lactamases - genetics / Bioinformatics / Biomedical and Life Sciences / Computer Science / Drug Resistance, Bacterial - genetics / Gastrointestinal Microbiome - genetics / Homology / Infectious Diseases / Intestinal microflora / Intestine / Intestines - microbiology / Life Sciences / Medical Microbiology / Microbiology / Microbiology and Parasitology / Microbiota / Parasitology / Pathogens / Protein Conformation / Virology
• ISBN: 0004530561000