Zebrafish Larvae as an; in vivo; Model for Antimicrobial Activity Tests against Intracellular; Salmonella;

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.; We established suitable; Salmonella; -infection conditions using genetically engineered zebrafish and; Salmonella; -expressing fluorescent proteins (; green fluorescent protein; (; GFP; ) and/or; mCherry; ).; 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.; 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.