M. tuberculosis (TB) is unrivalled in its capacity to infect humans and become drug-resistant. In New Zealand, a single case of a multidrug-resistant TB patient can cost the medical system $300,000 NZD. Meanwhile, China has the second largest burden of drug-resistant TB. Unlike other bacterial pathogens, the gold standard for tuberculosis therapy is a multitherapy of several distinct antibiotics. Despite the overwhelming evidence in favour of the use of multitherapies for all bacterial pathogens, the molecular mechanisms underlying antibiotic interactions are poorly understood. The goal of this study is therefore to become able to understand or predict antimicrobial synergy. A newly developed method, affinity based protein profiling (AfBP), can identify the secondary targets of antibiotics that may lead to antimicrobial synergy. In this application, we propose to combine AfBP with molecular biology approaches to understand antimicrobial synergy in TB, and therefore how combination therapy can be rationally designed.