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Prof Kathryn Holt

Professor of Microbial Systems Genomics

United Kingdom

Kat is a computational biologist specialising in infectious disease genomics. She has a BA/BSc (Hons) majoring in Biochemistry, Applied Statistics and Philosophy (University of Western Australia); a Master of Epidemiology (University of Melbourne); and a PhD in Molecular Biology (University of Cambridge and Sanger Institute).

Kat and her research team are particularly interested in the global health crisis of antimicrobial resistance (AMR), using genomic epidemiology tools to understand the evolutionary history and global dissemination of multidrug resistant pathogens, and developing new tools for prospective surveillance and tracking of emerging problems in the public health and clinical infectious disease space. They are also interested in human, animal and environmental microbiomes, and their role in chronic disease, infectious disease, and horizontal gene transfer.

Currently, a major focus of the group is genomic surveillance and epidemiology of Klebsiella pneumoniae, a pathogen recognised as critically important by the World Health Organisation due to its concerning levels of AMR. Together with collaborators, Kat's team uses genomics to investigate Klebsiella populations, primarily those causing infections in humans; and translate this growing knowledge base into the informatics tools Kaptive (for capsule (K) and O antigen serotype prediction), and Kleborate (for speciation, AMR and virulence typing), to support global research and surveillance activities.

Another key focus is Salmonella Typhi, the agent of typhoid fever. In addition to applying genomics to investigate typhoid epidemiology, Kat's group developed and maintain the GenoTyphi genotyping scheme; helped establish and coordinate the Global Typhoid Genomics Consortium (see typhoidgenomics.org) and developed the typhi.net dashboard for interactive visualisation of genomics-derived AMR and lineage data for Typhi.

Kat and team develop bioinformatics software when needed, and have developed lab and computational methods for nanopore sequencing. The research group adhere to open science principles - lab policy is to publish open access wherever possible, with preprints available before peer review; to deposit all data in public databases; and to release open source code.

Affiliations

Department of Infection Biology
Faculty of Infectious and Tropical Diseases

Centres

Antimicrobial Resistance Centre

Teaching

Kat is a Coordinator of the Short Course on Antimicrobial Resistance (AMR): a Multidisciplinary Approach

She and her team are also involved in MSc teaching, delivering lectures and workshops related to bacterial pathogen genomics in the Pathogen Genomics and Genomics Health Data modules.

Research

Kat’s research group uses computational genomics and sequencing, phylogenetics, spatiotemporal analysis and epidemiology to study the evolution and transmission of bacterial pathogens, including tropical diseases such as typhoid, dysentery, E. coli diarrhoea, and tuberculosis; and hospital associated pathogens such as Klebsiella and Acinetobacter.

Kat is particularly interested in the global health crisis of antimicrobial resistance (AMR), using genomic epidemiology tools to understand the evolutionary history and global dissemination of multidrug resistant pathogens, and developing new tools for prospective surveillance and tracking of emerging problems in the public health and clinical infectious disease space. Kat is also interested in human, animal and environmental microbiomes, and their role in chronic disease, infectious disease, and horizontal gene transfer.

Kat and her research team are particularly interested in the global health crisis of antimicrobial resistance (AMR), using genomic epidemiology tools to understand the evolutionary history and global dissemination of multidrug resistant pathogens, and developing new tools for prospective surveillance and tracking of emerging problems in the public health and clinical infectious disease space. They are also interested in human, animal and environmental microbiomes, and their role in chronic disease, infectious disease, and horizontal gene transfer.

Currently, a major focus of the group is genomic surveillance and epidemiology of Klebsiella pneumoniae, a pathogen recognised as critically important by the World Health Organisation due to its concerning levels of AMR. Together with collaborators, Kat's team uses genomics to investigate Klebsiella populations, primarily those causing infections in humans; and translate this growing knowledge base into the informatics tools Kaptive (for capsule (K) and O antigen serotype prediction), and Kleborate (for speciation, AMR and virulence typing), to support global research and surveillance activities.

Another key focus is Salmonella Typhi, the agent of typhoid fever. In addition to applying genomics to investigate typhoid epidemiology, Kat's group developed and maintain the GenoTyphi genotyping scheme; helped establish and coordinate the Global Typhoid Genomics Consortium (see typhoidgenomics.org) and developed the typhi.net dashboard for interactive visualisation of genomics-derived AMR and lineage data for Typhi.

Kat and team develop bioinformatics software when needed, and have developed lab and computational methods for nanopore sequencing. The research group adhere to open science principles - lab policy is to publish open access wherever possible, with preprints available before peer review; to deposit all data in public databases; and to release open source code.

Selected Publications

Diversity, functional classification and genotyping of SHV β-lactamases in<i>Klebsiella pneumoniae</i>
Tsang, K; Lam, MM C; Wick, R; Wyres, K; Bachman, M; Baker, S; Barry, K; Brisse, S; Campino, S; Chiaverini, A; Cirillo, DM; CLARK, T; Corander, J; Corbella, M; Cornacchia, A; Cuénod, A; D’Alterio, N; Di Marco, F; Donado-Godoy, P; Egli, A; Farzana, R; Feil, E; Fostervold, A; Gorrie, C; Gütlin, Y; ... KlebNET AMR Genotype-Phenotype Group,
2024
bioRxiv
Vaccine value profile for Klebsiella pneumoniae.
Dangor, Z; Benson, N; Berkley, JA; Bielicki, J; Bijsma, MW; Broad, J; Buurman, ET; Cross, A; Duffy, EM; HOLT, KE; Iroh Tam, P-Y; JIT, M; Karampatsas, K; Katwere, M; Kwatra, G; Laxminarayan, R; Le Doare, K; Mboizi, R; Micoli, F; Moore, CE; Nakabembe, E; NAYLOR, NR; O'Brien, S; Olwagen, C; Reddy, D; ... Madhi, SA.
2024
Vaccine
amrnet/amrnet: AMRnet-v1.0
CERDEIRA, L; Sharma, V; Maranga, M; CAREY, M; DYSON, ZA; HOLT, KE;
2024
Zenodo
Recent advances in modelling Shigella infection.
MILES, SL; HOLT, KE; MOSTOWY, S;
2024
Trends in microbiology
A validated pangenome-scale metabolic model for the <i>Klebsiella pneumoniae</i> species complex.
Cooper, HB; Vezina, B; Hawkey, J; Passet, V; López-Fernández, S; Monk, JM; Brisse, S; HOLT, KE; Wyres, KL;
2024
Microbial genomics
Evaluating the relationship between ciprofloxacin prescription and non-susceptibility in Salmonella Typhi in Blantyre, Malawi: an observational study.
Ashton, PM; Chunga Chirambo, A; Meiring, JE; Patel, PD; Mbewe, M; Silungwe, N; Chizani, K; Banda, H; Heyderman, RS; DYSON, ZA; MacPherson, P; Henrion, MY R; STRATAA Study Group,; HOLT, KE; Gordon, MA;
2024
The Lancet. Microbe
Pilot study to evaluate the need and implementation of a multifaceted nurse-led antimicrobial stewardship intervention in residential aged care
Jokanovic, N; Lee, SJ; Haines, T; Hilmer, SN; Jeon, Y-H; Travis, L; Ayton, D; Watson, E; Tsindos, T; Stewardson, AJ; Stuart, RL; Cheng, AC; Peel, TN; Peleg, AY; Peleg, A; Haines, T; Cheng, A; Peel, T; HOLT, K; Hilmer, S; Jeon, Y-H; Stewardson, A; Stuart, R; Lee, SJ; Wilson, D; ... Wisniewski, J.
2024
JAC-Antimicrobial Resistance
A validated pangenome-scale metabolic model for the<i>Klebsiella pneumoniae</i>species complex
Cooper, HB; Vezina, B; Hawkey, J; Passet, V; López-Fernández, S; Monk, JM; Brisse, S; HOLT, KE; Wyres, KL;
2023
Cold Spring Harbor Laboratory
Typhoid fever.
Meiring, JE; Khanam, F; Basnyat, B; Charles, RC; Crump, JA; Debellut, F; HOLT, KE; Kariuki, S; Mugisha, E; Neuzil, KM; Parry, CM; Pitzer, VE; Pollard, AJ; Qadri, F; Gordon, MA;
2023
Nature reviews. Disease primers
High-level nitrofurantoin resistance in a clinical isolate of <i>Klebsiella pneumoniae:</i> a comparative genomics and metabolomics analysis.
Hussein, M; Sun, Z; Hawkey, J; Allobawi, R; Judd, LM; Carbone, V; Sharma, R; Thombare, V; Baker, M; Rao, GG; Li, J; HOLT, KE; Velkov, T;
2023
mSystems
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