Next-generation approaches to understand and combat the antibiotic resistome

• Published in: Nature reviews. Microbiology Vol. 15; no. 7; pp. 422 - 434
• Main Authors: Crofts, Terence S., Gasparrini, Andrew J., Dantas, Gautam
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2017; Nature Publishing Group
• Subjects: 631/326/107; 631/326/22/1290; 631/326/22/1434; 631/326/2565/2142; Analysis; Anti-Bacterial Agents - pharmacology; Antibiotic resistance; Antibiotics; Bacteria; Bacteria - drug effects; Bacteria - genetics; Colistin; Communicable Diseases, Emerging - microbiology; Communicable Diseases, Emerging - prevention & control; Communicable Diseases, Emerging - therapy; Culture techniques; Drug resistance; Drug Resistance, Multiple, Bacterial - genetics; Ecosystems; Gene Transfer, Horizontal; Genes; Genes, Bacterial - drug effects; High-Throughput Nucleotide Sequencing; Horizontal transfer; Humans; Infectious Diseases; Life Sciences; Medical Microbiology; Metagenome - drug effects; Metagenomics - methods; Microbial drug resistance; Microbiology; Microorganisms; Parasitology; Phylogeny; Pure culture; review-article; Social aspects; Virology
• ISSN: 1740-1526; 1740-1534
• DOI: 10.1038/nrmicro.2017.28

Key Points The anthropogenic use of antibiotics has selected for an increase in the evolution and dissemination of antibiotic resistance in environmental and human-associated bacteria. The first generation of antibiotic resistance research coincided with the golden age of antibiotics and focused on single resistance genes in single (usually pathogenic) organisms. In recent decades, technical and computational advances in genomics and metagenomics have revealed widespread resistance across diverse microbial communities. Recent exceptional studies integrate a deep mechanistic understanding of resistance determinants with broad genomic analysis of microorganisms and microbial communities to improve both the surveillance of resistance threats and the proactive development of strategies to counter these threats. Antibiotic resistance is a global problem that threatens individual and societal well-being. In this Review, Crofts, Gasparrini and Dantas summarize how research has changed from the discovery of resistant bacteria to community-level resistome studies, and they propose future therapeutic and surveillance approaches. 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.