Injections of predatory bacteria work alongside host immune cells to treat Shigella Infection in zebrafish larvae

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Title: Injections of predatory bacteria work alongside host immune cells to treat Shigella Infection in zebrafish larvae
Author(s): Willis, A
Moore, C
Mazon Moya, M
Krokowski, S
Lambert, C
Till, R
Mostowy, S
Sockett, RE
Item Type: Journal Article
Abstract: Bdellovibrio bacteriovorus are predatory bacteria that invade and kill a range of Gram- negative bacterial pathogens in natural environments and in vitro [1, 2]. In this study we investigated Bdellovibrio as an injected, antibacterial-treatment, in vivo using zebrafish (Danio rerio) larvae infected with an antibiotic-resistant strain of the human pathogen Shigella flexneri. When injected alone Bdellovibrio can persist for more than 24 hours in vivo however exert no pathogenic effects on zebrafish larvae. Bdellovibrio injection of zebrafish containing a lethal dose of Shigella promotes pathogen killing, leading to increased zebrafish survival. Live-cell imaging of infected zebrafish reveals that Shigella undergo rounding induced by the invasive predation from Bdellovibrio in vivo. Furthermore, Shigella-dependent replication of Bdellovibrio was captured inside the zebrafish larvae indicating active predation in vivo. Bdellovibrio can be engulfed and ultimately eliminated by host neutrophils and macrophages, yet have a sufficient dwell time to prey upon pathogens. Experiments in immune-compromised zebrafish reveal that maximal therapeutic benefits of Bdellovibrio result from the synergy of both bacterial predation and host immunity, but that in vivo predation contributes significantly to the survival outcome. Our results demonstrate that successful antibacterial therapy can be achieved via the host immune system working together with bacterial predation by Bdellovibrio. Such cooperation may be important to consider in the fight against antibiotic resistant infections in vivo.
Publication Date: 23-Nov-2016
Date of Acceptance: 20-Sep-2016
URI: http://hdl.handle.net/10044/1/41193
DOI: https://dx.doi.org/10.1016/j.cub.2016.09.067
ISSN: 1879-0445
Publisher: Elsevier (Cell Press)
Start Page: 3343
End Page: 3351
Journal / Book Title: Current Biology
Volume: 26
Issue: 24
Copyright Statement: © 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Sponsor/Funder: Wellcome Trust
Lister Institute of Preventive Medicine
Funder's Grant Number: 097411/Z/11/ZR
n/a
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
BDELLOVIBRIO-BACTERIOVORUS
MODEL
Bdellovibrio
Shigella
antibacterial
antibiotic
innate immunity
predation
zebrafish
Developmental Biology
06 Biological Sciences
11 Medical And Health Sciences
17 Psychology And Cognitive Sciences
Publication Status: Published
Conference Place: United Kingdom
Appears in Collections:Department of Medicine
Faculty of Medicine



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