Department of Microbiology and Molecular Genetics, Rutgers New Jersey Medical School, 225 Warren Street, Newark, NJ 07107, United States.
Mutat Res. 2013 Sep;749(1-2):87-91. doi: 10.1016/j.mrfmmm.2013.07.009. Epub 2013 Aug 17.
The aminoglycoside streptomycin binds to ribosomes to promote mistranslation and eventual inhibition of translation. Streptomycin kills bacteria, whereas many other non-aminoglycoside inhibitors of translation do not. Because mistranslation is now known to affect DNA replication, we asked if hydroxyurea, a specific inhibitor of DNA synthesis, affects killing, and find that hydroxyurea significantly attenuates killing by streptomycin. We find that the hydroxyl radical scavengers d-mannitol and thiourea have either no effect or only a modest protective effect. The iron chelator 2,2'-dipyridyl eliminated killing by streptomycin, but further investigation revealed that it blocks streptomycin uptake. Prior treatment of cells with low-levels of methyl methanesulfonate to induce the adaptive response to alkylation leads to a significant attenuation of killing, which, together with the hydroxyurea effect, suggests roles for DNA replication and repair functions in cell killing by streptomycin.
氨基糖苷类链霉素与核糖体结合，促进翻译错误，最终抑制翻译。链霉素能杀死细菌，而许多其他非氨基糖苷类翻译抑制剂则不能。因为现在已经知道翻译错误会影响 DNA 复制，所以我们想知道 DNA 合成的特定抑制剂羟基脲是否会影响杀菌作用，并发现羟基脲显著减弱了链霉素的杀菌作用。我们发现，羟基自由基清除剂 D-甘露醇和硫脲没有影响或只有适度的保护作用。铁螯合剂 2,2'-联吡啶消除了链霉素的杀菌作用，但进一步的研究表明，它阻止了链霉素的摄取。先用低水平的甲磺酸甲酯处理细胞，诱导对烷化的适应性反应，导致杀菌作用显著减弱，这与羟基脲的作用一起表明，DNA 复制和修复功能在链霉素对细胞的杀伤中起作用。
