Sebastian Bruchmann, Theresa Feltwell, Julian Parkhill and Francesca Short: Pathogens and Disease Article Award 2021
Sebastian Bruchmann, Theresa Feltwell, Julian Parkhill and Francesca Short wrote the excellent research article “Identifying virulence determinants of multidrug-resistant Klebsiella pneumoniae in Galleria mellonella” for our Journal Pathogens and Disease. This was unanimously picked by the Pathogens and Disease Editors-in-Chiefs as the best article for 2021!
We interviewed all the authors to find out more about the inspiration behind this paper:
Could you provide a brief, simple overview of the topic your paper covers?
Our paper focuses on the bacterium Klebsiella pneumoniae and the genes required for its pathogenesis. K. pneumoniae is a major public health threat and is difficult to understand for a few reasons. One is that it is extremely diverse, so what underpins infection is not necessarily the same from strain to strain. Another reason is that K. pneumoniae strains that are not hypervirulent (which is the majority) generally do not cause disease in mice, so we are quite limited in terms of the models that can be used to study them.
In this study, we used high-throughput genomic fitness screening in an alternative in vivo model for infection – the caterpillar Galleria mellonella – to identify infection-related genes in a hypervirulent and a non-hypervirulent strain of K. pneumoniae. We found that certain known virulence factors have a dominant role in infection in both strains, but that, in addition, there are many putative virulence genes that contribute to infection only in the non-hypervirulent strain. These have been overlooked up to now because of a lack of suitable models for investigating non-hypervirulent K. pneumoniae.”
How important are model organisms in understanding K. pneumoniae pathogenesis?
Model organisms are extremely important for understanding bacterial pathogens and testing whether predictions from lab experiments hold up in vivo. It is important to remember that rodent models are not the be all and end all – there are different options, all with their own advantages and disadvantages. We hope that our study has illustrated the importance of considering alternative models when these are appropriate, and of conducting pathogenesis studies with an awareness of strain-to-strain differences rather than just assuming that infection-related processes will be the same in every member of a species.”
What encouraged you to perform research this area of microbiology?
We had several ongoing projects on K. pneumoniae pathogenesis, and our early results showed very clearly that different strains behaved in very different ways. So, we decided to explore this systematically.”
What do you see as the next steps in this area of research?
Important next steps from our study would be to investigate some of the strain-specific putative virulence genes we identified in more detail. It would also be interesting to expand this type of approach to additional lineages. More broadly, there is some very exciting work happening in the Klebsiella pathogenesis field aimed at developing models of infection that can be used for non-hypervirulent strains, and at combining genomics and other ‘-omic’ technologies with lab approaches to understand strain-specific modes of pathogenesis.”
Read the 2021 award winning paper: Identifying virulence determinants of multidrug-resistant Klebsiella pneumoniae in Galleria mellonella