Landscape of mobile genetic elements and their antibiotic resistance cargo in prokaryotic genomes

Author:

Khedkar Supriya1ORCID,Smyshlyaev Georgy12,Letunic Ivica3ORCID,Maistrenko Oleksandr M1ORCID,Coelho Luis Pedro4,Orakov Askarbek1,Forslund Sofia K1567,Hildebrand Falk1,Luetge Mechthild1,Schmidt Thomas S B1,Barabas Orsolya12ORCID,Bork Peer1589

Affiliation:

1. European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117 Heidelberg, Germany

2. Department of Molecular Biology, University of Geneva, 1211 Geneva, Switzerland

3. Biobyte solutions GmbH, Bothestr 142, 69117 Heidelberg, Germany

4. Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai 200433, China

5. Max Delbrück Centre for Molecular Medicine, Berlin, Germany

6. Experimental and Clinical Research Center, Charité-Universitätsmedizin and Max-Delbrück Center, Berlin, Germany

7. Charité – Universitätsmedizin Berlin, Berlin, Germany

8. Department of Bioinformatics, Biocenter, University of Würzburg, Würzburg, Germany

9. Yonsei Frontier Lab (YFL), Yonsei University, Seoul 03722, South Korea

Abstract

Abstract Prokaryotic Mobile Genetic Elements (MGEs) such as transposons, integrons, phages and plasmids, play important roles in prokaryotic evolution and in the dispersal of cargo functions like antibiotic resistance. However, each of these MGE types is usually annotated and analysed individually, hampering a global understanding of phylogenetic and environmental patterns of MGE dispersal. We thus developed a computational framework that captures diverse MGE types, their cargos and MGE-mediated horizontal transfer events, using recombinases as ubiquitous MGE marker genes and pangenome information for MGE boundary estimation. Applied to ∼84k genomes with habitat annotation, we mapped 2.8 million MGE-specific recombinases to six operational MGE types, which together contain on average 13% of all the genes in a genome. Transposable elements (TEs) dominated across all taxa (∼1.7 million occurrences), outnumbering phages and phage-like elements (<0.4 million). We recorded numerous MGE-mediated horizontal transfer events across diverse phyla and habitats involving all MGE types, disentangled and quantified the extent of hitchhiking of TEs (17%) and integrons (63%) with other MGE categories, and established TEs as dominant carriers of antibiotic resistance genes. We integrated all these findings into a resource (proMGE.embl.de), which should facilitate future studies on the large mobile part of genomes and its horizontal dispersal.

Funder

European Molecular Biology Laboratory

Federal Ministry of Education and Research

German Network for Bioinformatics Infrastructure

European Research Council

EMBARK JPIAMR

Shanghai Municipal Science and Technology

Publisher

Oxford University Press (OUP)

Subject

Genetics

Reference92 articles.

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