RT Journal Article SR Electronic T1 Prediction of the intestinal resistome by a novel 3D-based method JF bioRxiv FD Cold Spring Harbor Laboratory SP 196014 DO 10.1101/196014 A1 Etienne Ruppé A1 Amine Ghozlane A1 Julien Tap A1 Nicolas Pons A1 Anne-Sophie Alvarez A1 Nicolas Maziers A1 Trinidad Cuesta A1 Sara Hernando-Amado A1 Jose Luís Martínez A1 Teresa M. Coque A1 Fernando Baquero A1 Val F. Lanza A1 Luis Maiz A1 Tiphaine Goulenok A1 Victoire de Lastours A1 Nawal Amor A1 Bruno Fantin A1 Ingrid Wieder A1 Antoine Andremont A1 Willem van Schaik A1 Malbert Rogers A1 Xinglin Zhang A1 Rob J.L. Willems A1 Alexandre G. De Brevern A1 Jean-Michel Batto A1 Hervé Blottière A1 Pierre Léonard A1 Véronique Léjard A1 Aline Letur A1 Florence Levenez A1 Kevin Weiszer A1 Florence Haimet A1 Joël Doré A1 Sean P. Kennedy A1 S. Dusko Ehrlich YR 2017 UL http://biorxiv.org/content/early/2017/09/29/196014.abstract AB The intestinal microbiota is considered to be a major reservoir of antibiotic resistance determinants (ARDs) that could potentially be transferred to bacterial pathogens. Yet, this question remains hypothetical because of the difficulty to identify ARDs from intestinal bacteria. Here, we developed and validated a new annotation method (called pairwise comparative modelling, PCM) based on homology modelling in order to characterize the Human resistome. We were able to predict 6,095 ARDs in a 3.9 million protein catalogue from the Human intestinal microbiota. We found that predicted ARDs (pdARDs) were distantly related to known ARDs (mean amino-acid identity 29.8%). Among 3,651 pdARDs that were identified in metagenomic species, 3,489 (95.6%) were assumed to be located on the bacterial chromosome. Furthermore, genes associated with mobility were found in the neighbourhood of only 7.9% (482/6,095) of pdARDs. According to the composition of their resistome, we were able to cluster subjects from the MetaHIT cohort (n=663) into 6 “resistotypes”. Eventually, 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 support that most ARDs in the intestinal microbiota should be considered as intrinsic genes of commensal microbiota with a low risk of transfer to bacterial pathogens.