Antimicrobial resistance is a major international public health crisis. Central to this problem are drug-resistant strains of Mycobacterium tuberculosis, the causative agent of tuberculosis. Drug-resistant strains are difficult to treat, have long treatment times of >18 months, and cure rates of only 30-50%. However, drug resistance can have unintended impacts on bacterial cells, causing specific cellular pathways to become more important for the survival of drug-resistant strains and more vulnerable to targeted inhibition. We hypothesise that new antibiotics and antibiotic combinations that target these vulnerabilities will rapidly kill drug-resistant strains to drastically shorten the length of treatment and increase the success of clinical outcomes. To identify these vulnerabilities, we will establish a novel high-throughput functional genetic platform that will identify unique vulnerabilities and antibiotic combinations with a level of accuracy and throughput unmatched by classical drug screening.