Considering the two potential Corramycin uptake transporters SbmA and YejEF, we investigated the susceptibility of E. coli ATCC25922 with independent or combined deletion of those transporters in the animal model. The ED50s (effective dose for 50 % of the population) of the compound could not be evaluated in blood, because the tested doses were very efficacious for the wild type E. coli and the single deletion mutants. However, we could evaluate the ED50s in the spleen of the animals. The deletion of SbmA and YejEF in E. coli resulted in a mild decrease of susceptibility to Corramycin, affording ED50s of 23.3 mg kg -1 and 21.4 mg kg -1 , respectively, compared to the wild type control strain (6.1 mg kg -1 ). The double deletion of SbmA and YejEF, however, lead to a significant increase in resistance with an ED50 of >40 mg kg -1 . Taken together, Corramycin showed promising in vivo efficacy in a mouse septicemia model despite poor pharmacokinetic properties and a moderate MIC. The decreased susceptibility towards Corramycin in an E. coli strain lacking the SbmA and YejEF transporter systems resulted in an increased ED50 in the infected mice, thus complementing the results that we had obtained in our in vitro experiments.