The anti-tubercular callyaerins target the Mycobacterium tuberculosis-specific non-essential membrane protein Rv2113

Tuberculosis remains one of the most threatening bacterial infections, particularly due to the increasing prevalence of antibiotic-resistant strains of the pathogen Mycobacterium tuberculosis. Therefore, alternative antibiotics with divergent mechanisms of action are urgently required. Recently, callyaerin A and B, two derivatives of the callyaerins, a group of cyclic peptides bearing an unusual (Z)-2,3-diaminoacrylic acid unit, were identified as promising anti-tubercular natural products. Through a combination of spontaneous resistant mutant screening and affinity-based protein profiling (AfBPP) the non-essential but Mycobacterium tuberculosis-specific membrane protein Rv2113 was identified as the biological target of the callyaerins. However, the function of Rv2113 has not been fully resolved. Fluorescent microscopy experiments showed that Rv2113 is not involved in the cellular uptake of the callyaerins. Instead, our data indicate that Rv2113 is involved in mycobacterial lipid metabolism.