Our research
K. pneumoniae clone diversity and clinical risk
K. pneumoniae are extremely diverse. The population is divided into hundreds of distinct sub-groups (‘clones’) that are distantly related to each other and associated with different behaviours. No two K. pneumoniae contain the same set of genes; in fact, over half of each genome comprises so-called ‘accessory’ genes that vary from strain-to-strain and are drawn from a vast pool of more than 100,000 unique genes. As a result, individuals exhibit extensive variation in clinically-relevant traits such as drug-resistance, pathogenicity and virulence factors. Our work aims to understand how and why genomic diversity is structured in the K. pneumoniae population, and how this relates to strain- and clone- specific clinical risk e.g. the risk of causing different types of infection, evolving multi-drug resistance, or transmitting in the hospital setting. Specifically, we have projects focussing on:
- Developing a clone-specific genomic risk framework to systematically identify clinically-relevant clones and the frequencies with which they carry known antimicrobial resistance and virulence genes, and other key genetic traits.
- Identifying novel genomic and metabolic traits associated with multi-drug resistant strains, strains that are able to transmit in the hospital setting and strains that cause urinary tract infections – the most common type of K. pneumoniae infection among hospitalised patients.
- Understanding the relationship between clone diversity, ecology and metabolism.
Diversity and epidemiology of Klebsiella surface antigens
The polysaccharide capsule and lipopolysaccharide (LPS) surface antigens are targets for anti- K. pneumoniae vaccines and novel therapeutics. We developed Kaptive, a tool for the prediction of capsule and LPS variants from K. pneumoniae genome data, in collaboration with Kathryn Holt’s team (now at the London School of Hygiene and Tropical Medicine, UK). We are contining to improve the functionality and accuracy of Kaptive, develop new databases (e.g. for other Klebsiella species) and apply it to genome collections to predict capsule and LPS frequencies. Specifically, we are aiming to estimate the frequency distributions among Klebsiella causing neonatal sepsis in low- and middle- income countries, where K. pneumoniae is among the top three bacterial species causing this disease. We are also working with collaborators in academia and industry to generate new capsule phenotype data and develop approaches for predicting phenotypes from genome sequences.
KlebNET Genomic Surveillance Platform
We are contributors to the KlebNET Genomic Surveillance Platform (KlebNET-GSP) – a collaborative project with the aim to harmonise analysis tools and databases that support genomic surveillance of K. pneumoniae and related species in the K. pneumoniae species complex. KlebNET-GSP brings together the developers of the K. pneumoniae BIGSdb, Pathogen.watch global pathogen surveillance program, Kleborate and Kaptive. It also aims to develop training resources, promote and facilitate a lively community of researchers and public health professionals working on K. pneumoniae genomic epidemiology and surveillance.
Collaborators
We are extremely grateful to be able to work with talented and knowledgeable researchers from across the globe. Our key collaborators include:
- Prof Kathryn Holt – London School of Hygiene and Tropical Medicine, UK
- Dr Margaret Lam – Monash University, Australia
- Dr Jane Hawkey – Monash University, Australia
- Dr Adam Jenney – Alfred Health, Australia
- Dr Sylvain Brisse – Institut Pasteur, France
- Dr Jonathan Monk – University of California San Diego, USA
- Assoc Prof Johanna Kenyon – Griffith University
- Dr Iren Löhr – Stavanger University Hospital, Norway
- Prof Trevor Lithgow – Monash University, Australia
We are always happy to discuss new collaborative opportunities. If you have a project you would like to discuss, please contact us.
Funders
We thank the following organisations for supporting our research:
Current
- National Health and Medical Research Council, Australia
- Australian Research Council
- Bill and Melinda Gates Foundation
Past
- Australian Society for Antimicrobials
- University of Melbourne
Wyres lab 