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

Abstract

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.

Resistome metagenomics from plate to farm: the resistome and microbial composition during food waste feeding and composting on a Vermont poultry farm

“…In terms of clinical infection risk, many surveillance efforts track the occurrence of ESKAPE pathogens. EKSAPE pathogens ( Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa , and Enterobacter species) are responsible for the majority of nosocomial infections globally and can readily acquire antimicrobial resistance [45,46]. Pathogens on this list were identified in several samples in this study but did not persist or occur in any samples that would be leaving the farm or used in agricultural land application (Figure 6c).…”

Genomic characterization of an emerging Enterobacteriaceae species: the first case of co-infection with a typical pathogen in a human patient

“…The rapidly developing sequencing technology increasingly enables the identification of emerging opportunistic pathogens and taxonomical classification based on their genomic information [7][8][9]. Naturally, opportunistic pathogens inhabit in the natural environment and are occasionally resistant to common antibiotics.…”

Comprehensive antibiotic-linked mutation assessment by resistance mutation sequencing (RM-seq)

“…Multidrug-resistant bacteria are therefore becoming increasingly prevalent and drug susceptibility testing (DST) is now central to avoid antibiotic misuse and minimise the risk of inducing the emergence of new resistant clones. Over recent years, genomics has become a powerful tool to understand, combat and control the rise of resistance [2, 3]. Nevertheless, a precise definition of resistance at the genomic level is crucial to enable fast, culture-independent DST by high-throughput sequencing in the clinical context and to track and fight the spread and persistence of resistant clones globally [3, 4].…”

“…Over recent years, genomics has become a powerful tool to understand, combat and control the rise of resistance [2, 3]. Nevertheless, a precise definition of resistance at the genomic level is crucial to enable fast, culture-independent DST by high-throughput sequencing in the clinical context and to track and fight the spread and persistence of resistant clones globally [3, 4]. …”