Tuberculosis can be treated with antibiotics. However, a combination of four drugs over a time period of 6-month is required. Still, antibiotic-resistance strains have evolved, making treatment even more difficult. We study drug discovery using two different approaches. The first approach is to identify compounds that block T7S. As there are several essential T7S systems, we hypothesize that blocking multiple systems would decrease the possibility of resistance development. In an international consortium we are in the process of identifying ESX-5 inhibitors. The second approach is to study antibiotic stress systems, which are upregulated when the bacteria are confronted with sublethal amounts of antibiotics. These stress genes could be used as biomarkers for drug development but also as drug targets themselves, if they contribute to bacterial survival under stress conditions. One stress system that has been studied in detail is the IniBAC system that is induced upon addition of ethambutol and isoniazid, antibiotics that both target cell envelope biogenesis.