Context-aware genomic surveillance reveals hidden transmission of a carbapenemase-producing Klebsiella pneumoniae

Abstract

Genomic surveillance can inform effective public health responses to pathogen outbreaks. However, integration of non-local data is rarely done. We investigate two large hospital outbreaks of a carbapenemase-carrying Klebsiella pneumoniae strain in Germany and show the value of contextual data. By screening about 10 000 genomes, over 400 000 metagenomes and two culture collections using in silico and in vitro methods, we identify a total of 415 closely related genomes reported in 28 studies. We identify the relationship between the two outbreaks through time-dated phylogeny, including their respective origin. One of the outbreaks presents extensive hidden transmission, with descendant isolates only identified in other studies. We then leverage the genome collection from this meta-analysis to identify genes under positive selection. We thereby identify an inner membrane transporter (ynjC) with a putative role in colistin resistance. Contextual data from other sources can thus enhance local genomic surveillance at multiple levels and should be integrated by default when available.

Sourmash Branchwater Enables Lightweight Petabyte-Scale Sequence Search

“…K-mer search via branchwater has been used in two projects so far - Lumian et al (2022) [16] and Viehweger et al (2021) [15]. Viehweger et al used branchwater to find a metagenome containing an additional Klebsiella pneumoniae for a large scale analysis of outbreak data, while Lumian et al conducted a global biogeography analysis of five new antarctic cyanobacteria.…”

“…The availability of relatively lightweight content-based search of SRA metagenomes helps address many of the biological use cases in Table 1 (see 3rd column). Some of these use cases have already been explored with Branchwater: Viehweger et al (2021) [15] used Branchwater to discover a metagenomic sample containing Klebsiella pneumonia that was subsequently included in an outbreak analysis, and Lumian et al (2022) [16] conducted a biogeographical study on five newly generated cyanobacterial genomes from Antarctic samples.…”

Long-Read Whole Genome Sequencing Elucidates the Mechanisms of Amikacin Resistance in Multidrug-Resistant Klebsiella pneumoniae Isolates Obtained from COVID-19 Patients

“…At the same time, various factors limit the ability to analyze the putative outbreak genomes in real-time, which, surprisingly, might include not the restrictions imposed by sequencing technologies, but rather data management and bioinformatics, for example, the lack of common outbreak repositories and delays between data collection and computational analysis [ 44 , 45 ]. Thus, creating more sophisticated bioinformatics tools can also advance AMR prevention strategies and the epidemiological surveillance of K. pneumoniae and other important pathogens.…”

Dissemination of a single ST11 clone of OXA-48-producing Klebsiella pneumoniae within a large polyclonal hospital outbreak determined by genomic sequencing

“…This underlines the importance of active high resolution (i.e. genomic) surveillance programmes [44,45] because in the context of a large hospital-wide epidemic, neither the outbreaks nor the transmission between wards can be correctly differentiated with lower resolution typing methods (such as MLST or PFGE). Genome sequencing has already become fast and cheap enough to be used extensively for rapid epidemiological surveillance, tracking of transmission pathways and guiding infection control.…”