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

Raghunathan, D., Radford, P.M., Gell, C., Negus, D. ORCID: 0000-0001-9047-4565, Moore, C., Till, R., Tighe, P.J., Wheatley, S.P., Martinez-Pomares, L., Sockett, R.E. and Tyson, J., 2019. Engulfment, persistence and fate of Bdellovibrio bacteriovorus predators inside human phagocytic cells informs their future therapeutic potential. Scientific Reports, 9: 4293. ISSN 2045-2322

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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 specifc 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.

Item Type: Journal article
Publication Title: Scientific Reports
Creators: Raghunathan, D., Radford, P.M., Gell, C., Negus, D., Moore, C., Till, R., Tighe, P.J., Wheatley, S.P., Martinez-Pomares, L., Sockett, R.E. and Tyson, J.
Publisher: Nature Research
Date: 12 March 2019
Volume: 9
ISSN: 2045-2322
Identifiers:
NumberType
10.1038/s41598-019-40223-3DOI
Rights: © The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Divisions: Schools > School of Science and Technology
Depositing User: Jill Tomkinson
Date Added: 14 Mar 2019 11:05
Last Modified: 14 Mar 2019 11:05
URI: http://irep.ntu.ac.uk/id/eprint/35997

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