Challenges and opportunities for whole-genome sequencing-based surveillance of antibiotic resistance

Infections caused by drug-resistant bacteria are increasingly reported across the planet, and drug-resistant bacteria are recognized to be a major threat to public health and modern medicine. In this review, we discuss how whole-genome sequencing (WGS)-based approaches can contribute to the surveillance of the emergence and spread of antibiotic resistance. We outline the characteristics of sequencing technologies that are currently most used for WGS (Illumina short-read technologies and the long-read sequencing platforms developed by Pacific Biosciences and Oxford Nanopore). The challenges posed by the analysis of sequencing data sets for antimicrobial-resistance determinants and the solutions offered by modern bioinformatics tools are discussed. Finally, we illustrate the power of WGS-based surveillance of antimicrobial resistance by summarizing recent studies on the spread of the multidrug-resistant opportunistic pathogen Klebsiella pneumoniae and the transferable colistin-resistance gene mcr-1, in which high-throughput WGS analyses played essential roles. The implementation of WGS for surveillance of antibiotic-resistant bacteria is technically feasible and cost effective and provides actionable results with reference to infection control. Consequently, the time has come for laboratories to implement routine genome sequencing as part of their surveillance programs for antibiotic-resistant bacteria.