Kokoczka Rachel, Schuessler Dorothée L, Early Julie V, Parish Tanya
TB Discovery Research, Infectious Disease Research Institute, 1616 Eastlake Ave E, Suite 400, Seattle, WA, 98102, United States.
Queen Mary University of London, Barts and the London School of Medicine and Dentistry, London, E1 2AD, UK.
Tuberculosis (Edinb). 2017 Jan;102:3-7. doi: 10.1016/j.tube.2016.11.001. Epub 2016 Nov 5.
Mycobacterium tuberculosis Rv0560c, a putative benzoquinone methyl transferase, is heavily induced in response to salicylate exposure. It has some similarity to Escherichia coli UbiG, although its role in ubiquinone or menaquinone synthesis is not clear, since M. tuberculosis is not known to produce ubiquinone. We constructed an unmarked in-frame deletion of Rv0560c in M. tuberculosis to determine its role in vitro. Deletion of Rv0560c in M. tuberculosis had no effect on growth in medium containing salicylate or in its ability to grow in macrophages. In addition, no change to compound sensitivity, as determined by minimum inhibitory concentrations, for a range of compounds targeting respiration was noted. Plumbagin, ethambutol and CCCP had the same minimum bactericidal concentration against the deletion and wild-type strains. Taken together these data show that Rv0560c is dispensable under in vitro conditions in both axenic and macrophage culture and suggest that the role of Rv0560c may be in an alternate biosynthetic pathway of menaquinone which is only used under specific growth conditions.
结核分枝杆菌Rv0560c是一种假定的苯醌甲基转移酶,在暴露于水杨酸盐时会大量被诱导。它与大肠杆菌UbiG有一些相似之处,尽管其在泛醌或甲萘醌合成中的作用尚不清楚,因为已知结核分枝杆菌不产生泛醌。我们构建了结核分枝杆菌Rv0560c的无标记框内缺失菌株,以确定其在体外的作用。结核分枝杆菌中Rv0560c的缺失对其在含水杨酸盐培养基中的生长或在巨噬细胞中的生长能力没有影响。此外,通过最低抑菌浓度测定,针对一系列靶向呼吸作用的化合物,其化合物敏感性没有变化。白花丹素、乙胺丁醇和CCCP对缺失菌株和野生型菌株具有相同的最低杀菌浓度。综合这些数据表明,在体外条件下,无论是在无菌培养还是巨噬细胞培养中,Rv0560c都是可有可无的,这表明Rv0560c的作用可能在于甲萘醌的另一条生物合成途径,该途径仅在特定生长条件下使用。