**Aaron Go**ff**, Daire Cantillon, Leticia Muraro Wildner and Simon J Waddell \***

Department of Global Health and Infection, Brighton and Sussex Medical School, University of Sussex, Brighton BN1 9PX, UK; A.Goff@bsms.ac.uk (A.G.); D.Cantillon2@bsms.ac.uk (D.C.);

L.MuraroWildner@bsms.ac.uk (L.M.W.)

**\*** Correspondence: s.waddell@bsms.ac.uk; Tel.: +44-1273-87-7572

Received: 28 May 2020; Accepted: 30 June 2020; Published: 3 July 2020

**Abstract:** Multi-omics strategies are indispensable tools in the search for new anti-tuberculosis drugs. Omics methodologies, where the ensemble of a class of biological molecules are measured and evaluated together, enable drug discovery programs to answer two fundamental questions. Firstly, in a discovery biology approach, to find new targets in druggable pathways for target-based investigation, advancing from target to lead compound. Secondly, in a discovery chemistry approach, to identify the mode of action of lead compounds derived from high-throughput screens, progressing from compound to target. The advantage of multi-omics methodologies in both of these settings is that omics approaches are unsupervised and unbiased to a priori hypotheses, making omics useful tools to confirm drug action, reveal new insights into compound activity, and discover new avenues for inquiry. This review summarizes the application of *Mycobacterium tuberculosis* omics technologies to the early stages of tuberculosis antimicrobial drug discovery.

**Keywords:** mycobacterium; tuberculosis; drug discovery; genomics; transcriptomics; proteomics; metabolomics; lipidomics; target identification; mechanism of action; antimicrobial drug resistance (AMR)
