Science:甲基修饰抑制TLR13识别23S rRNA引发细菌耐药

7月19日，Science在线报道，TLR13受体可识别一类保守的23S核糖体RNA序列，以及一种围绕该相互作用的细菌耐药机制。

保护宿主免受感染的机制依赖于识别受体，如Toll样受体（TLRs），以与生俱来的模式识别病原体。

本研究证实，在小鼠体内，孤儿受体TLR13识别一个细菌内保守的23S核糖体RNA（rRNA）序列。该序列是大环内酯类，林肯酰胺以及链霉杀阳菌素类（MLS）抗生素（包括红霉素）的结合位点。

值得注意的是，源自从临床分离的耐红霉素金黄色葡萄球菌的23S rRNA和带甲基化腺苷或鸟苷的合成寡核苷酸可模拟导致 MLS抵抗的修饰。此修饰的结果是不能激活TLR13。

总之，该研究结果发现了一个天然TLR13配体，以及一种引发抗生素耐药性的具体机制。该机制通过避免TLR13介导的识别，作为细菌强有力的免疫逃避策略。

doi:10.1016/j.cell.2011.10.017
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TLR13 Recognizes Bacterial 23S rRNA Devoid of Erythromycin Resistance–Forming Modification

Marina Oldenburg1,*,Anne Krüger1,*,Ruth Ferstl2,*,?,Andreas Kaufmann3,Gernot Nees3,Anna Sigmund1,Barbara Bathke4,Henning Lauterbach4,Mark Suter4,5,Stefan Dreher2,Uwe Koedel6,Shizuo Akira7,Taro Kawai7,Jan Buer1,Hermann Wagner2,Stefan Bauer3,Hubertus Hochrein4,*,Carsten J. Kirschning

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 S. aureus and synthetic oligoribonucleotides carrying methylated adenosine or a guanosine mimicking a MLS resistance–causing modification failed to stimulate TLR13. Our results thus reveal both a natural TLR13 ligand and specific mechanisms of antibiotic resistance as potent bacterial immune evasion strategy, avoiding recognition via TLR13.