KlebNET-GSP
A global genomic surveillance platform for Klebsiella pneumoniae
KlebNET-GSP develops resources to support genomic surveillance for Klebsiella pneumoniae and related bacterial pathogens.
We also aim to develop an international network of scientists involved in Klebsiella research and build capacity in genomics.
News
What is Klebsiella pneumoniae?
Klebsiella pneumoniae is a Gram-negative bacterium and a major human pathogen. It is part of a species complex (KpSC) which also comprises other disease-causing species including Klebsiella quasipneumoniae and Klebsiella variicola.
K. pneumoniae and the related species cause a wide range of infections that can be hospital-acquired (HA) such as sepsis, pneumonia, urinary tract and wound infections. These occur most commonly among neonates, the elderly and immunocompromised patients. Naturally resistant to penicillins, many K. pneumoniae have also acquired resistance to numerous other drugs, with high rates of resistance to third-generation cephalosporins and carbapenems amongst HA infections. In many settings treatment options have become extremely limited, with reliance on older more toxic drugs (like colistin or tigecycline) or new expensive drugs (like beta-lactamase combination drugs, and cefiderocol).
K. pneumoniae is also responsible for community-acquired (CA) infections, including pneumonia, endophthalmitis and pyogenic liver abscess. These infections are often severe and can occur in otherwise healthy individuals. CA isolates commonly carry a repertoire of extra virulence genes such as siderophores. Moreover, infections involving strains with high levels of both resistance and virulence have now also been reported, leading to international concern over a potential rise of serious untreatable infections.
Members of the species complex, including K. pneumoniae, are also important agents of disease in animals, particularly in livestock (e.g. bovine mastitis). They are isolated at high rates from environmental and water samples. It is therefore pivotal to apply a One Health approach to Klebsiella research and genomic surveillance in order to fully understand the ecology of these pathogens.
Why does Klebsiella matter? Some key facts
- The Global burden of Antimicrobial Resistance (AMR) identified K. pneumoniae as one of just six organisms with an attributable burden estimated to exceed 100,000 AMR deaths in 2021.
- K. pneumoniae was most significant in children under 5 years, in whom deaths associated with Streptococcus pneumoniae have reduced dramatically thanks to the introduction of pneumococcal vaccines.
- Overall, K. pneumoniae was estimated to be responsible for 19.4% of AMR-attributable deaths in the under-5s, and 12.7% of AMR-attributable deaths in people aged 5 years and older.
The World Health Organisation classifies K. pneumoniae as the most critical priority pathogen for which new antibiotics are urgently needed.
What can we do about Klebsiella?
- New treatments: K. pneumoniae is a priority for GARD-P (the Global Antibiotic Research & Development Partnership) and CARB-X (Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator fund), who are supporting new therapeutic strategies against the pathogen and other Gram-negative bacteria. There is also growing interest in phage therapy against Klebsiella.
- Prevention: The K. pneumoniae Vaccine Value Profile describes two potential vaccine strategies: a vaccine delivered to pregnant women in LMIC to protect the fetus and young infant; and a worldwide vaccine for vulnerable children, adolescent and adult populations identified as at risk of K. pneumoniae infection (e.g. due to malnutrition, being immunocompromised, or intensive healthcare exposures). The World Health Organisation rated a maternal vaccine against K. pneumoniae with 70% efficacy and 70% coverage as ‘medium feasibility’ but with high impact, estimated to avert 27,500 neonatal deaths annually, reducing antibiotic use by 210,000 daily doses and saving $US279 million in hospital costs.
- Infection control: K. pneumoniae spreads easily in hospitals and healthcare facilities, causing local and regional epidemics. Strengthening infection prevention and control (IPC) is crucial to reduce hospital-associated infections with K. pneumoniae and other pathogens, and pathogen genomics can greatly enhance IPC investigations.
All of these strategies can be supported and enhanced by genomic surveillance.
Genomic surveillance
Genomic surveillance has become fundamental to our understanding of pathogen ecology and disease dynamics. For K. pneumoniae, genomic surveillance is a useful tool to monitor which lineages are causing disease in different countries and settings (HA or CA), and how these lineages are emerging and evolving, particularly with regards to acquisition of antimicrobial resistance and virulence genes. It can also be used to assess the diversity of serological markers, including K (capsule) and O antigens (LPS), which are potential vaccine candidates.
The availability of harmonised platforms for global genomic surveillance is key to developing a common understanding of pathogen evolution and emerging risks, and to informing control strategies – this is what we aim to achieve with KlebNET-GSP.
We envisage that our combined scientific and technical advances will facilitate reporting of Klebsiella for public health surveillance at local, national and global scales, enabling crucial development and monitoring of interventions (e.g., vaccines).
KlebNET Tools
Kleborate is a tool to screen genome assemblies of the K. pneumoniae species complex for genotypic markers that are of clinical and public health importance. It can be run on the command-line or via the Pathogenwatch application, and its AMR and virulence gene schemes are integrated within BIGSdb-Pasteur.
Further details can be found in the associated publication and user documentation.
Pathogenwatch is a web application that provides tailored genome analytics for a range of bacterial (and other) species, including those from the Klebsiella pneumoniae species complex, as well as visualisation tools for the integration of these analytics with epidemiological data.
Further details can be found in the associated publication and user documentation.
BIGSdb-Pasteur is a web-based platform that hosts a collection of curated databases of genome sequences and genotypes and provides universally accessible nomenclatures for referencing and comparing bacterial strains.
The platform is built on the BIGSdb software developed by Keith Jolley. Further information can be found in the associated publication and user documentation.
Please refer to Kaptive for capsule and LPS locus typing of Klebsiella, further information can be found in the associated publication and user documentation.
LIN codes, a novel approach for Genomic Taxonomy of Bacterial strains
LIN codes are numerical codes given to bacteria based on genomic fingerprinting With LIN codes, every bacterial strain has its own identifier (a short code similar to a barcode) which is easy to share and use and also indicates how much different strains are related to each other. Using LIN codes is a great way to make epidemiological surveillance simpler, more flexible and more reactive.
For full LIN codes concept, please watch a general public video at: https://www.youtube.com/watch?v=xRqydUyLcr8
please visit the genomic taxonomy platform BIGSb-Pasteur: https://bigsdb.pasteur.fr/
(see also : Preprint by Palma et al., bioRxiv, 2024)
Other KlebNET Resources
The Training page has plenty of learning resources including tutorials and videos to help you learn how to use KlebNET tools.
Lab protocols for isolating, identifying and sequencing Klebsiella are available on our protocols.io site.
Curated genome data collections:
Data standards:
Collaborative Consortium Projects
We coordinate collaborative consortia and meta-analyses related to Klebsiella genomics, aiming to strengthen the evidence base for interpreting genomic surveillance data. This includes the KlebNET-GSP AMR Genotype/Phenotype Consortium exploring the interpretation of antimicrobial resistance genotypes; as well as groups focused on developing a genomic risk framework, neonatal sepsis antigen distributions, and neonatal sepsis transmission dynamics
Principal Investigators
David Aanensen
Professor, Oxford
Andrew McArthur
David Braley Chair, McMaster
Angela Dramowski
Professor, Stellenbosch
Sascha Ott
Professor, Warwick
Andrew Whitelaw
Professor, Stellenbosch
KlebNET Team
Links & Contacts
Supported by the University of Oxford, Institut Pasteur and the London School of Hygiene & Tropical Medicine
Funded in part by the Gates Foundation
