Institute of Medical Microbiology, University of Duisburg-Essen, Essen, Germany.
Science. 2012 Aug 31;337(6098):1111-5. doi: 10.1126/science.1220363. Epub 2012 Jul 19.
Host protection from infection relies on the recognition of pathogens by innate pattern-recognition receptors such as Toll-like receptors (TLRs). Here, we show that the orphan receptor TLR13 in mice recognizes a conserved 23S ribosomal RNA (rRNA) sequence that is the binding site of macrolide, lincosamide, and streptogramin group (MLS) antibiotics (including erythromycin) in bacteria. Notably, 23S rRNA from clinical isolates of erythromycin-resistant Staphylococcus aureus and synthetic oligoribonucleotides carrying methylated adenosine or a guanosine mimicking a MLS resistance-causing modification failed to stimulate TLR13. Thus, our results reveal both a natural TLR13 ligand and specific mechanisms of antibiotic resistance as potent bacterial immune evasion strategy, avoiding recognition via TLR13.
宿主通过先天模式识别受体（如 Toll 样受体 (TLR)）识别病原体，从而获得抗感染保护。在这里，我们发现小鼠中的孤儿受体 TLR13 识别细菌中 23S 核糖体 RNA（rRNA）的保守序列，该序列是大环内酯类、林可酰胺类和链阳性菌素类（MLS）抗生素（包括红霉素）的结合位点。值得注意的是，红霉素耐药金黄色葡萄球菌临床分离株的 23S rRNA 和携带甲基化腺苷或模拟 MLS 耐药致变修饰的鸟嘌呤的合成寡核糖核苷酸均不能刺激 TLR13。因此，我们的结果揭示了天然 TLR13 配体和抗生素耐药的特定机制，作为一种有效的细菌免疫逃避策略，通过 TLR13 避免识别。
