Rapid Genomic Characterization and Global Surveillance of Klebsiella Using Pathogenwatch

Abstract

Background: Klebsiella species, including the notable pathogen K. pneumoniae, are increasingly associated with antimicrobial resistance (AMR). Genome-based surveillance can inform interventions aimed at controlling AMR. However, its widespread implementation requires tools to streamline bioinformatic analyses and public health reporting.

Methods: We developed the web application Pathogenwatch, which implements analytics tailored to Klebsiella species for integration and visualization of genomic and epidemiological data. We populated Pathogenwatch with 16 537 public Klebsiella genomes to enable contextualization of user genomes. We demonstrated its features with 1636 genomes from 4 low- and middle-income countries (LMICs) participating in the NIHR Global Health Research Unit (GHRU) on AMR.

Results: Using Pathogenwatch, we found that GHRU genomes were dominated by a small number of epidemic drug-resistant clones of K. pneumoniae. However, differences in their distribution were observed (eg, ST258/512 dominated in Colombia, ST231 in India, ST307 in Nigeria, ST147 in the Philippines). Phylogenetic analyses including public genomes for contextualization enabled retrospective monitoring of their spread. In particular, we identified hospital outbreaks, detected introductions from abroad, and uncovered clonal expansions associated with resistance and virulence genes. Assessment of loci encoding O-antigens and capsule in K. pneumoniae, which represent possible vaccine candidates, showed that 3 O-types (O1-O3) represented 88.9% of all genomes, whereas capsule types were much more diverse.

Conclusions: Pathogenwatch provides a free, accessible platform for real-time analysis of Klebsiella genomes to aid surveillance at local, national, and global levels. We have improved representation of genomes from GHRU participant countries, further facilitating ongoing surveillance.

Keywords: Klebsiella; Pathogenwatch; antimicrobial resistance; epidemiology; genomic surveillance.

Figure 1.

Overview of the analytical processes performed on Klebsiella genomes and the available visualizations in Pathogenwatch. Abbreviations: AMR, antimicrobial resistance; MLST, multi-locus sequence typing.

Figure 2.

Pathogenwatch shows different dynamics of transmission and dissemination of the dominant “high risk” lineages in each GHRU participant country. ST258 genomes from Colombia form 1 main phylogenetic cluster, suggestive of a single successful introduction (A). ST231 genomes from India (B), ST307 genomes from Nigeria (C), and ST147 genomes from the Philippines (D) all form multiple phylogenetic clusters, suggesting multiple origins. The map insets show the widespread distribution of these clones in each country. Abbreviations: GHRU, Global Health Research Unit; ST, sequence type.

Figure 3.

Pathogenwatch demonstrates convergence of virulence and resistance in a phylogenetic tree of 308 ST231 genomes from the public and GHRU collections (clade indicated with an asterisk (*). (A) The tree and map are filtered via the search bar by the presence of the virulence determinant aerobactin (iuc). All aerobactin-positive isolates are indicated with a circular node in the tree (red or white). Red nodes indicate the additional presence of the OXA-232 carbapenemase gene. Pie charts on the map show the relative proportion of aerobactin-positive isolates with and without OXA-232. (B) The tree and map are filtered via the search bar by the presence of replicon sequence ColKP3. ColKP3-positive isolates are indicated with purple nodes in the tree. (C) Likely acquisition of virulence loci (yersiniabactin and aerobactin) and plasmid-borne resistance (OXA-232 and ColKP3) followed by clonal expansion of the clade indicated with an asterisk (*). Abbreviations: GHRU, Global Health Research Unit; ST, sequence type.