Capreomycin is a second-line
drug for multiple-
drug-resistant tuberculosis (TB). However, with increased use in clinics, the therapeutic efficiency of
capreomycin is decreasing. To better understand TB resistance to
capreomycin, we have done research to identify the molecular target of
capreomycin. Mycobacterium tuberculosis
ribosomal proteins L12 and L10 interact with each other and constitute the stalk of the 50S ribosomal subunit, which recruits initiation and elongation factors during translation. Hence, the L12-L10 interaction is considered to be essential for ribosomal function and
protein synthesis. Here we provide evidence showing that
capreomycin inhibits the L12-L10 interaction by using an established L12-L10 interaction assay. Overexpression of L12 and/or L10 in M. smegmatis, a species close to M.
tuberculosis, increases the MIC of
capreomycin. Moreover, both
elongation factor G-dependent
GTPase activity and ribosome-mediated
protein synthesis are inhibited by
capreomycin. When
protein synthesis was blocked with
thiostrepton, however, the bactericidal activity of
capreomycin was restrained. All of these results suggest that
capreomycin seems to inhibit TB by interrupting the L12-L10 interaction. This finding might provide novel clues for anti-TB
drug discovery.