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Science 337 (6098): 1111-1115

Copyright © 2012 by the American Association for the Advancement of Science

TLR13 Recognizes Bacterial 23S rRNA Devoid of Erythromycin Resistance–Forming Modification

Marina Oldenburg,1,* Anne Krüger,1,* Ruth Ferstl,2,*,{dagger} Andreas Kaufmann,3 Gernot Nees,3 Anna Sigmund,1 Barbara Bathke,4 Henning Lauterbach,4 Mark Suter,4,5 Stefan Dreher,2 Uwe Koedel,6 Shizuo Akira,7 Taro Kawai,7 Jan Buer,1 Hermann Wagner,2 Stefan Bauer,3 Hubertus Hochrein,4,* Carsten J. Kirschning1,*,{ddagger}

Abstract: 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.

1 Institute of Medical Microbiology, University of Duisburg-Essen, 45147 Essen, Germany.
2 Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, 81675 Munich, Germany.
3 Institute for Immunology, Philipps University of Marburg, 35043 Marburg, Germany.
4 Department of Research Immunology, Bavarian Nordic GmbH, 82152 Martinsried, Germany.
5 Institute of Virology, University of Zurich, 8006 Zurich, Switzerland.
6 Department of Neurology, Clinic of the University of Munich, 81377 Munich, Germany.
7 World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.

* These authors contributed equally to this work.

{dagger} Present address: Swiss Institute of Allergy and Asthma Research, University of Zurich, 7270 Davos, Switzerland.

{ddagger} To whom correspondence should be addressed. E-mail: carsten.kirschning{at}uk-essen.de


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