Zebrafish Larvae as an Model for Antimicrobial Activity Tests against Intracellular .

Introduction: Blood infections from multi-drug-resistant pose a major health burden. This is especially true because can survive and replicate intracellularly, and the development of new treatment strategies is dependent on expensive and time-consuming trials. The aim of this study was to develop a -infection model that makes it possible to directly observe infections of macrophages and to use this model to test the effect of antimicrobials against intra- and extracellular in order to close the gap between and rodent-infection models.

Methods: We established suitable -infection conditions using genetically engineered zebrafish and -expressing fluorescent proteins ( () and/or ).

Results: We detected inside and outside zebrafish larvae macrophages. Administration of the cell-impermeable antibiotic tobramycin removed residing outside macrophages but did not affect in macrophages, whereas ceftriaxone successfully cleared both types of . 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 in a complex environment. This model thus might serve for antimicrobial lead optimization prior to using rodent models.