IMR Press / FBL / Volume 28 / Issue 5 / DOI: 10.31083/j.fbl2805099
Open Access Original Research
Zebrafish Larvae as an in vivo Model for Antimicrobial Activity Tests against Intracellular Salmonella
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1 Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, 4056 Basel, Basel-Stadt, Switzerland
2 Institute of Chemistry and Biotechnology, Zurich University of Applied Sciences (ZHAW), 8820 Wädenswil Zürich, Switzerland
3 Focal Area Infection Biology, Biozentrum, University of Basel, 4056 Basel, Basel-Stadt, Switzerland
*Correspondence: (Jörg Huwyler)
Front. Biosci. (Landmark Ed) 2023, 28(5), 99;
Submitted: 23 February 2023 | Revised: 12 April 2023 | Accepted: 26 April 2023 | Published: 25 May 2023
(This article belongs to the Special Issue Role of Zebrafish in Human Disease Research)
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Introduction: Blood infections from multi-drug-resistant Salmonella pose a major health burden. This is especially true because Salmonella can survive and replicate intracellularly, and the development of new treatment strategies is dependent on expensive and time-consuming in vivo trials. The aim of this study was to develop a Salmonella-infection model that makes it possible to directly observe Salmonella infections of macrophages in vivo and to use this model to test the effect of antimicrobials against intra- and extracellular Salmonella in order to close the gap between in vitro and rodent-infection models. Methods: We established suitable Salmonella-infection conditions using genetically engineered zebrafish and Salmonella-expressing fluorescent proteins (green fluorescent protein (GFP) and/or mCherry). Results: We detected Salmonella inside and outside zebrafish larvae macrophages. Administration of the cell-impermeable antibiotic tobramycin removed Salmonella residing outside macrophages but did not affect Salmonella in macrophages, whereas ceftriaxone successfully cleared both types of Salmonella. Salmonella inside and outside macrophages experienced substantial DNA damage after administration of fluoroquinolones consistent with the excellent cell penetration of these antibiotics. Conclusions: The zebrafish-larvae model enables testing of antimicrobials for efficacy against extra- and intracellular Salmonella in a complex in vivo environment. This model thus might serve for antimicrobial lead optimization prior to using rodent models.

Salmonella enterica
zebrafish larvae
antibiotic resistance
drug screening
Graphical Abstract
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SCAHT-GL 21-09/Swiss Centre for Applied Human Toxicology – SCAHT
SNIP1801/Swiss Nanoscience Institute
Fig. 1.
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