Measuring and modelling the response of Klebsiella pneumoniae KPC prey to Bdellovibrio bacteriovorus predation, in human serum and defined buffer

Baker, Michelle; Negus, David; Raghunathan, Dhaarini; Radford, Paul; Moore, Christopher; Clark, Gemma; Diggle, Mathew; Tyson, Jess; Twycross, Jamie; Sockett, R. Elizabeth

Abstract

In worldwide conditions of increasingly antibiotic-resistant hospital infections, it is important to research alternative therapies. Bdellovibrio bacteriovorus bacteria naturally prey on Gram-negative pathogens, including antibiotic-resistant strains and so B. bacteriovorus have been proposed as “living antibiotics” to combat antimicrobially-resistant pathogens. Predator-prey interactions are complex and can be altered by environmental components. To be effective B. bacteriovorus predation needs to work in human body fluids such as serum where predation dynamics may differ to that studied in laboratory media. Here we combine mathematical modelling and lab experimentation to investigate the predation of an important carbapenem-resistant human pathogen, Klebsiella pneumoniae, by B. bacteriovorus in human serum versus buffer. We show experimentally that B. bacteriovorus is able to reduce prey numbers in each environment, on different timescales. Our mathematical model captures the underlying dynamics of the experimentation, including an initial predation-delay at the predator-preyserum interface. Our research shows differences between predation in buffer and serum and highlights both the potential and limitations of B. bacteriovorus acting therapeutically against K. pneumoniae in serum, informing future research into the medicinal behaviours and dosing of this living antibacterial.

Citation

Baker, M., Negus, D., Raghunathan, D., Radford, P., Moore, C., Clark, G., …Sockett, R. E. (in press). Measuring and modelling the response of Klebsiella pneumoniae KPC prey to Bdellovibrio bacteriovorus predation, in human serum and defined buffer. Scientific Reports, 7(8329), https://doi.org/10.1038/s41598-017-08060-4

• Journal Article Type: Article
• Acceptance Date: Jul 4, 2017
• Online Publication Date: Aug 21, 2017
• Deposit Date: Aug 22, 2017
• Publicly Available Date: Aug 22, 2017
• Journal: Scientific Reports
• Electronic ISSN: 2045-2322
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 7
• Issue: 8329
• DOI: https://doi.org/10.1038/s41598-017-08060-4
• Keywords: Bdellovibrio, Pathogen, Serum, Klebsiella, modelling
• Public URL: https://nottingham-repository.worktribe.com/output/878536
• Publisher URL: http://www.nature.com/articles/s41598-017-08060-4
• Related Public URLs: https://www.nature.com/articles/s41598-017-08060-4
• Contract Date: Aug 22, 2017