3.3.1. MptpB Inhibitors

The *M. tuberculosis* protein-tyrosine-phosphatase B (MptpB) is another putative target for anti-virulence compounds (Figure 1). This kinase is secreted into the cytoplasm of host macrophages allowing for inhibition outside the thick and difficult to overcome mycobacterial cell wall [111]. The function of MptpB is not fully described yet, but the protein has been reported to be necessary for bacterial survival in guinea pigs [112]. So far, it was shown that MptpB dephosphorylates host phosphotyrosine substrates, phosphoserine/threonine substrates and phosphoinositides, with the latter being essential for host macrophage maturation [113].

Several isoxazole-based molecules were created to block the primary and secondary phosphate-binding pockets of MptpB followed by phenotypic testing for activity. In these ex vivo assays, the compounds led to a reduction of mycobacterial burden in macrophages (J774 and THP-1) and in a guinea pig model, without affecting extracellular growth in broth. Additionally, attenuated growth of MDR strains of *M. tuberculosis* in the presence of compound 13 was shown in macrophages. In addition, this inhibitor caused increased sensitivity of a BCG strain to rifampicin and isoniazid in an ex vivo macrophage infection experiment [114]. A similar effect has not been published for *M. tuberculosis* yet.
