Neomycin and paromomycin inhibit 30S ribosomal subunit assembly in Staphylococcus aureus
Neomycin and paromomycin inhibit 30S ribosomal subunit assembly in Staphylococcus aureus
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DOI：
10.1007/s00284-002-3945-9
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发表时间：
2003-09-01
影响因子：
2.6
通讯作者：
Champney, WS
中科院分区：
文献类型：
--
作者：
Mehta, R;Champney, WS
许多通过与细菌细胞的50 S核糖体亚基结合来阻止翻译的不同抗生素最近被证明也阻止了该亚基的组装。影响30 S颗粒活性的抗菌剂尚未广泛研究对小亚基形成的影响。氨基糖苷类抗生素巴龙霉素和新霉素特异性结合30 S核糖体亚基并抑制翻译。在金黄色葡萄球菌细胞中检查这些药物，以观察它们是否对30 S颗粒组装具有第二抑制作用。使用H-3-尿苷脉冲和追踪测定来检查在存在和不存在每种抗生素的情况下亚基合成的动力学。30 S亚基的形成被两种化合物抑制。与对照细胞相比，每种抗生素在3 μ g/mL时使30 S形成率降低80%。两种抗生素均表现出浓度依赖性的颗粒形成抑制，对50 S颗粒形成的影响较小。对于新霉素，30 S颗粒形成的IC 50等于抑制翻译的IC 50。两种抗生素均降低活细胞数，IC 50为2 μ g/mL。它们还以不同的IC 50值（2.5和1.25 mug/mL）抑制细胞中的蛋白质合成。这是第二次证明30 S核糖体亚基特异性抗生素可以阻止小亚基的组装。
A number of different antibiotics that prevent translation by binding to the 50S ribosomal subunit of bacterial cells have recently been shown to also prevent assembly of this subunit. Antibacterial agents affecting 30S particle activities have not been examined extensively for effects on small subunit formation. The aminoglycoside antibiotics paromomycin and neomycin bind specifically to the 30S ribosomal subunit and inhibit translation. These drugs were examined in Staphylococcus aureus cells to see whether they had a second inhibitory effect on 30S particle assembly. A H-3-uridine pulse and chase assay was used to examine the kinetics of subunit synthesis in the presence and absence of each antibiotic. 30S subunit formation was inhibited by both compounds. At 3 mug/mL each antibiotic reduced the rate of 30S formation by 80% compared with control cells. Both antibiotics showed a concentration-dependent inhibition of particle formation, with a lesser effect on 50S particle formation. For neomycin, the IC50 for 30S particle formation was equal to the IC50 for inhibition of translation. Both antibiotics reduced the viable cell number with an IC50 of 2 mug/mL. They also inhibited protein synthesis in the cells with different IC50 values (2.5 and 1.25 mug/mL). This is the second demonstration of 30S ribosomal subunit-specific antibiotics that prevent assembly of the small subunit.