Impact of Drug Administration Routes on the In Vivo Efficacy of the Natural Product Sorangicin a Using aInfection Model in Zebrafish Embryos.

Abstract

causes a wide range of infections, and it is one of the leading pathogens responsible for deaths associated with antimicrobial resistance, the rapid spread of which amongurges the discovery of new antibiotics. The evaluation of in vivo efficacy of novel drug candidates is usually performed using animal models. Recently, zebrafish () embryos have become increasingly attractive in early drug discovery. Herein, we established a zebrafish embryo model ofinfection for evaluation of in vivo efficacy of novel potential antimicrobials. A local infection was induced by microinjecting mCherry-expressingNewman followed by treatment with reference antibiotics via microinjection into different injection sites as well as via waterborne exposure to study the impact of the administration route on efficacy. We successfully used the developed model to evaluate the in vivo activity of the natural product sorangicin A, for which common mouse models were not successful due to fast degradation in plasma. In conclusion, we present a novel screening platform for assessing in vivo activity at the antibiotic discovery stage. Furthermore, this work provides consideration for the choice of an appropriate administration route based on the physicochemical properties of tested drugs.