Wyres Group

Bacterial population genomics and metabolism

Overview

We are a computational microbiology group using comparative genomics and genome-scale metabolic modelling to understanding the evolution and epidemiology of bacterial pathogens. We develop and apply computational tools to large genome datasets, and are primarily focussed on Klebsiella pneumoniae- a World Health Organization priority antimicrobial resistant pathogen, for which novel control strategies are urgently required. This species is particularly interesting because it is 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.

Group Head

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Our work is divided into two themes

  1. Understanding the drivers of K. pneumoniae clone diversity and clone-specific clinical risk: K. pneumoniae’s extensive clone diversity represents a biological puzzle: It is not known how or why so many clones have evolved and continue to exist in the population. Our team is using a novel combination of genomics and comparative genome-scale metabolic modelling to shed light on this biological phenomenon. We are also using association studies to identify K. pneumoniae genetic and metabolic markers of clinical risk, such as the risk of causing particular types of infection, evolving multi-drug resistance, or causing outbreaks in the hospital setting. With this knowledge we will inform next-generation genomic surveillance and stream-lined infection control practices.
  2. Understanding the diversity and epidemiology of Klebsiella surface antigens: The capsule and lipopolysaccharide surface antigens are targets for anti- K. pneumoniae vaccines and novel therapeutics. We developed Kaptive, a tool for the prediction of antigen variants from K. pneumoniae genome data in collaboration with Kathryn Holt’s lab at the London School of Hygiene and Tropical Medicine. Kaptive is now used in research and public health labs globally. We are continually working to improve the functionality and accuracy of Kaptive, and apply it to genome collections to predict antigen frequencies. These data are directly informing the design of novel vaccines targeting K. pneumoniae.

Publications

See GoogleScholar for a full list of publications.

Further information

Visit the Wyres lab website to find out more about research work and team.