Whole-Genome Sequencing of Bacterial Pathogens: the Future of Nosocomial Outbreak Analysis

Abstract

Outbreaks of multidrug-resistant bacteria present a frequent threat to vulnerable patient populations in hospitals around the world. Intensive care unit (ICU) patients are particularly susceptible to nosocomial infections due to indwelling devices such as intravascular catheters, drains, and intratracheal tubes for mechanical ventilation. The increased vulnerability of infected ICU patients demonstrates the importance of effective outbreak management protocols to be in place. Understanding the transmission of pathogens via genotyping methods is an important tool for outbreak management. Recently, whole-genome sequencing (WGS) of pathogens has become more accessible and affordable as a tool for genotyping. Analysis of the entire pathogen genome via WGS could provide unprecedented resolution in discriminating even highly related lineages of bacteria and revolutionize outbreak analysis in hospitals. Nevertheless, clinicians have long been hesitant to implement WGS in outbreak analyses due to the expensive and cumbersome nature of early sequencing platforms. Recent improvements in sequencing technologies and analysis tools have rapidly increased the output and analysis speed as well as reduced the overall costs of WGS. In this review, we assess the feasibility of WGS technologies and bioinformatics analysis tools for nosocomial outbreak analyses and provide a comparison to conventional outbreak analysis workflows. Moreover, we review advantages and limitations of sequencing technologies and analysis tools and present a real-world example of the implementation of WGS for antimicrobial resistance analysis. We aimed to provide health care professionals with a guide to WGS outbreak analysis that highlights its benefits for hospitals and assists in the transition from conventional to WGS-based outbreak analysis.

Keywords: bioinformatics; intensive care units; next-generation sequencing; nosocomial infections; outbreak analysis; outbreak management; pathogen surveillance; point of care; whole-genome sequencing.

FIG 1

Simplified SCS construction.

FIG 2

Simplified k-mer construction during de Bruijn graph assembly.

FIG 3

WGS outbreak analysis tools. Different steps in the analysis of WGS data are shown in orange (assembly, genomic characterization, comparative genomics, and phylogeny). Analysis tools are grouped by the analysis step that they perform and are separated by user interface in shades of blue (complete analysis software suites, Web based, and command line).