To achieve first insights related to in vivo efficacy of MyxA for chemotherapy of tuberculosis during the acute stage of infection, C57Bl/6 mice were aerosol-infected with ~300 M. tuberculosis bacilli and daily treatment at 2 mg/kg (i.p.) initiated after 10 days. Unfortunately, the MyxA-treated group became moribund after one week of daily treatment and the study had to be terminated. Based on organ burden enumeration in lung and spleen, no significant effect on bacterial burden was observed (Fig. ). The non-curing and toxic effects of MyxA in this mouse model can be possibly explained by two factors. Firstly, although blood levels are in the range of in vitro MIC against M. tuberculosis MyxA might not reach infected tissue sites at sufficient levels. Secondly, the low drug clearance and observed in vivo toxicity at doses > 2 mg/kg/d in combination with pathophysiology of M. tuberculosis infection might potentiate overall toxicity as observed after one week in the mouse model of tuberculosis. Nevertheless, both issues could be addressed by modification of the MyxA scaffold following the established total synthetic route with the overall goal to reduce off-target toxicity and improve (oral) bioavailability and lung exposure.