title: Next-generation approaches to understand and combat the antibiotic resistome.
abstract: Antibiotic resistance is a natural feature of diverse microbial ecosystems. Although recent studies of the antibiotic resistome have highlighted barriers to the horizontal transfer of antibiotic resistance genes between habitats, the rapid global spread of genes that confer resistance to carbapenem, colistin and quinolone antibiotics illustrates the dire clinical and societal consequences of such events. Over time, the study of antibiotic resistance has grown from focusing on single pathogenic organisms in axenic culture to studying antibiotic resistance in pathogenic, commensal and environmental bacteria at the level of microbial communities. As the study of antibiotic resistance advances, it is important to incorporate this comprehensive approach to better inform global antibiotic resistance surveillance and antibiotic development. It is increasingly becoming apparent that although not all resistance genes are likely to geographically and phylogenetically disseminate, the threat presented by those that are is serious and warrants an interdisciplinary research focus. In this Review, we highlight seminal work in the resistome field, discuss recent advances in the studies of resistomes, and propose a resistome paradigm that can pave the way for the improved proactive identification and mitigation of emerging antibiotic resistance threats.
authors.affiliation: Center for Genome Sciences &Systems Biology, Washington University School of Medicine, 4515 McKinley Avenue, Campus Box 8510, St. Louis, Missouri 63110, USA.
authors.forename: Terence S
authors.initials: TS
authors.lastname: Crofts
authors.affiliation: Center for Genome Sciences &Systems Biology, Washington University School of Medicine, 4515 McKinley Avenue, Campus Box 8510, St. Louis, Missouri 63110, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Gasparrini
authors.affiliation: Center for Genome Sciences &Systems Biology, Washington University School of Medicine, 4515 McKinley Avenue, Campus Box 8510, St. Louis, Missouri 63110, USA.|Department of Pathology and Immunology, Washington University School of Medicine.|Department of Molecular Microbiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.|Department of Biomedical Engineering, Washington University in St. Louis, 1 Brookings Drive, St. Louis, Missouri 63130, USA.
authors.forename: Gautam
authors.initials: G
authors.lastname: Dantas
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics; D021821:Communicable Diseases, Emerging / Q000382:microbiology / Q000517:prevention & control / Q000628:therapy; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D022761:Gene Transfer, Horizontal; D005798:Genes, Bacterial / Q000187:drug effects; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D054892:Metagenome / Q000187:drug effects*; D056186:Metagenomics / Q000379:methods; D010802:Phylogeny
chemical_list: D000900:Anti-Bacterial Agents