An indigenous posttranscriptional modification in the ribosomal peptidyl transferase center confers resistance to an array of protein synthesis inhibitors.
An indigenous posttranscriptional modification in the ribosomal peptidyl transferase center confers resistance to an array of protein synthesis inhibitors.
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DOI：
10.1016/j.jmb.2008.05.027
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发表时间：
2008-07
影响因子：
5.6
通讯作者：
Seok-Ming Toh;A. Mankin
中科院分区：
文献类型：
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作者：
Seok-Ming Toh;A. Mankin
核糖体RNA(RRNA)中的许多核苷酸残基经历了特定的转录后修饰。大多数修饰的作用尚不清楚，但它们聚集在rRNA的功能重要区域表明，它们可能直接影响核糖体的活性，或调节其与配体的相互作用。在大肠杆菌23S rRNA中的25个修饰核苷酸中，有14个位于肽基转移酶中心，该中心是大核糖体亚基的主要抗生素靶点。由于核苷酸修饰与抗生素敏感性和抗生素耐药性密切相关，其中一些转录后修饰的缺失可能会影响细菌对抗生素的敏感性。我们研究了针对肽基转移酶中心的8种rRNA修饰酶基因失活的大肠杆菌细胞对抗生素的敏感性。23S rRNA的2504位缺失假尿苷可显著增加细菌对肽基转移酶抑制剂的敏感性。因此，这种天然的转录后修饰可能已经演变为保护细菌对天然抗生素的内在耐药机制。
A number of nucleotide residues in ribosomal RNA (rRNA) undergo specific posttranscriptional modifications. The roles of most modifications are unclear, but their clustering in functionally important regions of rRNA suggests that they might either directly affect the activity of the ribosome or modulate its interactions with ligands. Of the 25 modified nucleotides in Escherichia coli 23S rRNA, 14 are located in the peptidyl transferase center, the main antibiotic target in the large ribosomal subunit. Since nucleotide modifications have been closely associated with both antibiotic sensitivity and antibiotic resistance, loss of some of these posttranscriptional modifications may affect the susceptibility of bacteria to antibiotics. We investigated the antibiotic sensitivity of E. coli cells in which the genes of 8 rRNA-modifying enzymes targeting the peptidyl transferase center were individually inactivated. The lack of pseudouridine at position 2504 of 23S rRNA was found to significantly increase the susceptibility of bacteria to peptidyl transferase inhibitors. Therefore, this indigenous posttranscriptional modification may have evolved as an intrinsic resistance mechanism protecting bacteria against natural antibiotics.