NHMRC Emerging Leadership Fellow
I am interested in understanding the evolution of bacteria through exploring their DNA. I use comparative genomics techniques and genome-scale metabolic modelling to investigate the evolution and epidemiology of Klebsiella pneumoniae, a bacterial pathogen that causes large numbers of healthcare-associated infections and is associated with high rates of antimicrobial resistance. I am particularly interested in the differences between closely related groups of strains, or ‘clones,’ that seem to be associated with distinct behaviours e.g. see my recent study comparing the genomic evolutionary histories of 28 different clones.
I am currently leading two major projects:
A clone-specific risk framework for Klebsiella pneumoniae transmission and AMR
The overarching goal here is to identify K. pneumoniae genetic and metabolic traits that are associated with clinically relevant risks e.g. the risk of causing a specific type of infection, of becoming drug-resistant or of transmitting in the hospital. In so doing, I hope to inform novel treatment and infection control strategies that limit the burden of K. pneumoniae disease.
Funding: NHMRC Investigator Grant; ASA Research Grant
Unlocking the secrets of metabolic variation in a highly diverse bacterium
This project aims to characterise K. pneumoniae metabolic diversity, and understand how it is associated with the evolutionary history and ecology of this bacterium.
Funding: ARC Discovery Project
My computational microbiology journey
I joined the Holt Lab in September 2015 as a Post-Doctoral Research Fellow. My early work was focussed on understanding the genetics and diversity of the K. pneumoniae capsule synthesis locus, which encodes the outer polysaccharide capsule – a key virulence factor and vaccine target. As part of this work I co-developed a tool called Kaptive for rapid capsule locus typing from Klebsiella genome data, which is now used by many researchers around the globe and available online at Kaptive Web.
Prior to joining the Holt lab I spent 2 ½ years as a Staff Researcher at IBM Research – Australia. I was a founding member of the IBM Research – Australia Genomics Team and later became the Team Lead. My team was interested in exploring the use of computing for clinical and public health genomics. We collaborated with colleagues around the world and contributed to a number of applied and pure research projects, including an evolutionary exploration of drug resistant Mycobacterium tuberculosis.
Before moving to Australia and joining IBM, I completed my Bachelor’s and Doctoral degrees at the University of Oxford, UK. During my DPhil (doctoral degree), I studied the genomic evolution of Streptococcus pneumoniae under the supervision of Prof Angela Bruggemann. I focused on the evolution of penicillin resistance and capsule switching, the latter of which has implications for the design of S. pneumoniae vaccines. Between my undergraduate and post-graduate studies I worked with Dr Mike Bonsall, investigating the epidemiology of Bacillus thuringiensis and the interaction with its host, the Diamond Back Moth.
*For a full list of my publications see my Google Scholar profile.
- Wyres, K.L., Nguyen, T.N.T., Lam, M.M.C., Judd, L.M., van Vinh Chau, N., Dance, D.A.B., Ip, M., Karkey, A., Ling, C.L., Miliya, T., Newton, P., Nguyen, L., Sengduangphachanh, A., Turner, P., Veeraraghavan, B., Vinh, P.V., Vongsouvath, M., Thomson, N.R., Baker, S. and Holt, K.E. 2019. Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from south and southeast Asia. bioRxiv doi: https://doi.org/10.1101/557785.
- Wyres K.L., Wick R.R., Judd L.M., Froumine R., Tokolyi A., Gorrie C.L., Lam M.M.C, Duchêne S., Jenney A. and Holt K.E. Distinct evolutionary dynamics of horizontal gene transfer in drug resistant and virulent clones of Klebsiella pneumoniae. PLoS Genetics 15(4): e1008114.
- Lam, M.M.C.† / Wyres, K.L.†, Duchene, S., Wick, R.R., Judd, L.M., Gan Y-H., Hoh, C-H., Archuleta, S., Molten, J.S., Kalimuddin, S., Koh, T.H., Passet, V., Brisse, S. and Holt K.E. 2018. Population genomics of hypervirulent Klebsiella pneumoniae clonal-group 23 revelas early emergence and rapid global dissemination. Nature Communications 9:2703. †Co-first authors.
- Lam, M.M.C., Wick, R.R., Wyres, K.L., Gorrie, C.L., Judd, L.M., Jenney, A.W.J., Brisse, S. and Holt, K.E. 2018. Genetic diversity, mobilisation and spread of the yersiniabactin-encoding mobile element ICEKp in Klebsiella pneumoniae populations. Microbial Genomics 4.
- Wyres, K.L.† / Hawkey, J.,† Hetland, M.K.A., Fostervold A., Wick, R.R., Judd, L.M., Hamidian, M., Howden, B.P., Lohr, I.H. and Holt, K.E. 2018. Emergence and rapid global dissemination of CTX-M-15-associated Klebsiella pneumoniae strain ST307. Journal of Antimicrobial Chemotherapy 74:577-581. † Co-first authors.
- Wyres K.L. and Holt, K.E. 2018. Klebsiella pneumoniae as a key trafficker of drug resistance genes from environmental to clinically relevant bacteria. Current Opinion in Microbiology 45:131-139.
- Wick, R.R., Heinz, E., Holt, K.E. and Wyres, K.L. 2018. Kaptive Web: user-friendly capsule and lipopolysaccharide serotype prediction for Klebsiella genomes. Journal of Clinical Microbiology 56:e00197-18.
- Wyres, K.L. and Holt K.E. 2016. Klebsiella pneumoniae population genomics and antimicrobial resistant clones. Trends in Microbiology 24(12):944-956.
- Wyres, K.L, Wick, R.R., Gorrie, C., Jenney, A., Follador, R., Thomson, N.R. and Holt, K.E. 2016. Identification of Klebsiella capsule synthesis loci from whole genome data. Microbial Genomics 2.
- Follador, R., Heinz, E., Wyres, K.L., Ellington, M.J., Kowarik, M., Holt, K.E. and Thomson, N.R. 2016. The diversity of Klebsiella pneumoniae surface polysaccharides. Microbial Genomics 2.
- Wyres, K.L., Gorrie, C., Edwards, D.J., Wertheim, H.F.L., Hsu, L.Y., Van Kinh, N., Zadoks, R., Baker, S. and Holt, K.E. 2015. Extensive capsule locus variation and large-scale genomic recombination within the Klebsiella pneumoniae clonal group 258. Genome Biology and Evolution 7(5), 1267-1279.
- Wyres, K.L., Lambertsen, L.M., Croucher, N.J., McGee, L., von Gottberg, A., Liñares, J., Jacobs, M. R., Kristinsson, K.G., Beall, B.W., Klugman, K.P., Parkhill, J., Hakenbeck, H., Bentley, S.D. and Brueggemann, A.B. 2013. Pneumococcal capsular switching: An historical perspective. Journal of Infectious Disease 207:439-449.
- Raymond, B.† / Wyres, K.L.†, Sheppard, S.K., Ellis, R.J. and Bonsall, M.B. 2010. Environmental factors determining the epidemiology and population genetic structure of the Bacillus cereus group in the field. PLoS Pathogens 6:5, e1000905.† Co-first authors.