PhD, Professor of Microbial Systems Genomics, London School of Hygiene & Tropical Medicine

Kat Holt earned 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)

Humans have been investigating this dynamic and diverse population of microorganisms ever since Antonie van Leeuwenhoek discovered the presence of microbes under his microscope for the first time in 1673. The more discoveries are made, the more challenges and unknowns occur. Currently, one of the urgent problems in the field is the emergence of microbial pathogens that have gained antimicrobial resistance. The increase in multidrug-resistant pathogens may render existing therapies useless, and the risk for medical procedures could increase greatly. Dr.Kat Holt and her lab at The University of London investigate a variety of pathogens and their antimicrobial resistance using an array of computational biology tools, in hopes to monitor future outbreaks through genomic surveillance.

One of the pathogens that she focuses on is Klebsiella pneumoniae. While it is naturally found in the human microbiome, it is also an opportunistic pathogen that accounts for approximately 11.8% of nosocomial outbreaks worldwide (Ashurst & Dawson, 2022). They are often found to target hospitalized patients with pre-existing conditions, however, more virulent strains of K. pneumoniae are being discovered, and this raise concerns that it will spread into healthy individuals as well (Paczosa & Mecsas, 2016). The increase in antimicrobial resistance found in K. pneumoniae strains threatens the efficacy of traditional antimicrobial treatments. Dr. Holt’s recent publication have thoroughly analyzed the genomic content of various k. pneumoniae strains and have found the convergence of hypervirulent and antimicrobial resistance genes in certain strains (Holt et al., 2015). Additionally, she also proposed that k. pneumoniae not only acts as a pathogen, but also a trafficker that transfers virulent and antimicrobial resistance genes to other pathogens as well (Wyres & Holt, 2018). These findings all justify the immediate importance for genomic surveillance of pathogens to track and predict its next move.

Outside of conducting genomic analysis, Dr. Holt is also interested in developing novel bioinformatics tools. SRST2, along with several other software, is one of the software that her team has developed for rapid identification of pathogens and its genomic components. SRST2 can quickly identify the presence of specific genes, which proves to be useful when it comes to identifying if a pathogen has any antimicrobial resistance (Inouye et al., 2014). Currently, SRST2 is incorporated as a routine tool for genomic analysis in many public healthy agencies worldwide, including Canada (Inouye et al., 2014). In the world where microbial pathogens are always diverse and ever-changing, Dr. Holt’s work is much needed.

References

– Ashurst, J. v., & Dawson, A. (2022). Klebsiella Pneumonia. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK519004/

– Holt, K. E., Wertheim, H., Zadoks, R. N., Baker, S., Whitehouse, C. A., Dance, D., Jenney, A., Connor, T. R., Hsu, L. Y., Severin, J., Brisse, S., Cao, H., Wilksch, J., Gorrie, C., Schultz, M. B., Edwards, D. J., Nguyen, K. van, Nguyen, T. V., Dao, T. T., … Thomson, N. R. (2015). Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health. Proceedings of the National Academy of Sciences, 112(27), E3574–E3581. https://doi.org/10.1073/pnas.1501049112

– Inouye, M., Dashnow, H., Raven, L.-A., Schultz, M. B., Pope, B. J., Tomita, T., Zobel, J., & Holt, K. E. (2014). SRST2: Rapid genomic surveillance for public health and hospital microbiology labs. Genome Medicine, 6(11), 90. https://doi.org/10.1186/s13073-014-0090-6

– Paczosa, M. K., & Mecsas, J. (2016). Klebsiella pneumoniae: Going on the Offense with a Strong Defense. Microbiology and Molecular Biology Reviews, 80(3), 629–661. https://doi.org/10.1128/MMBR.00078-15/FORMAT/EPUB

– Wyres, K. L., & Holt, K. E. (2018). Klebsiella pneumoniae as a key trafficker of drug resistance genes from environmental to clinically important bacteria. Current Opinion in Microbiology, 45, 131–139. https://doi.org/https://doi.org/10.1016/j.mib.2018.04.004