Engulfment, persistance and fate of Bdellovibrio bacteriovorus predators inside human phagocytic cells informs their future therapeutic potential

Raghunathan, Dhaarini; Radford, Paul M.; Gell, Christopher; Negus, David; Moore, Christopher; Till, Rob; Tighe, Patrick J.; Wheatley, Sally P.; Martinez-Pomares, Luisa; Elizabeth Sockett, R.; Tyson, Jess

Abstract

In assessing the potential of predatory bacteria, such as Bdellovibrio bacteriovorus, to become live therapeutic agents against bacterial infections, it is crucial to understand and quantify Bdellovibrio host cell interactions at a molecular level. Here
we quantify the interactions of live B. bacteriovorus with human phagocytic cells, determining the uptake mechanisms, persistence, associated cytokine responses and intracellular trafficking of the non-growing B. bacteriovorus in PMA-differentiated U937 cells. B. bacteriovorus are engulfed by U937 cells and persist for 24h without affecting host cell viability and can be observed microscopically and recovered and cultured post-uptake. The uptake of predators is passive and depends on the dynamics of the host cell cytoskeleton; the engulfed predators are eventually trafficked through the phagolysosomal pathway of degradation. We have also studied the prevalence of B. bacteriovorus specific antibodies in the general human population. Together, these results quantify a period of viable persistence and the ultimate fate of B. bacteriovorus inside phagocytic cells. They provide new knowledge on predator availability inside hosts, plus potential longevity and therefore potential efficacy as a treatment in humans and open up future fields of work testing if predators can prey on host-engulfed pathogenic bacteria.

Citation

Raghunathan, D., Radford, P. M., Gell, C., Negus, D., Moore, C., Till, R., Tighe, P. J., Wheatley, S. P., Martinez-Pomares, L., Elizabeth Sockett, R., & Tyson, J. (2019). Engulfment, persistance and fate of Bdellovibrio bacteriovorus predators inside human phagocytic cells informs their future therapeutic potential. Scientific Reports, 9, 1-16. https://doi.org/10.1038/s41598-019-40223-3

• Journal Article Type: Article
• Acceptance Date: Feb 11, 2019
• Online Publication Date: Mar 12, 2019
• Publication Date: Mar 12, 2019
• Deposit Date: Feb 13, 2019
• Publicly Available Date: Mar 12, 2019
• Journal: Scientific Reports
• Electronic ISSN: 2045-2322
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Article Number: 4293
• Pages: 1-16
• DOI: https://doi.org/10.1038/s41598-019-40223-3
• Public URL: https://nottingham-repository.worktribe.com/output/1544033
• Publisher URL: https://www.nature.com/articles/s41598-019-40223-3
• Contract Date: Feb 13, 2019