Bacterial 23S rRNA is recognized by the endosomal TLR13 unless it is modified to constitute erythromycin resistance
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1
University of Duisburg-Essen, Institute of Medical Microbiology, Germany
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2
University of Zurich, Swiss Institute of Allergy and Asthma Research (SIAF), Switzerland
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3
Philipps University of Marburg, Institute for Immunology, Germany
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4
Technical University of Munich, Institute of Medical Microbiology, Immunology and Hygiene, Germany
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5
Bavarian Nordic GmbH, Department of Research Immunology, Germany
The innate immune system, being very sensitive, tends to over-amplify inflammatory signals. Accordingly, bacterial infections often cause septic shock. Major intiators of sepsis are bacterial infections with Escherichia coli and Staphylococcus aureus. Analyzing their interaction with the host, we observed recognition of a segment within bacterial 23S ribosomal (r) RNA through TLR13 in mice. The same segment is a target for antibiotics like macrolide, lincosamide and streptogramin group (MLS) antibiotics (including erythromycin). As a resistance mechanism bacteria prevent binding of MLS antibiotics to 23S rRNA by inducing N-methylation at a specific adenosine (A) upon acquisition of a distinct erythromycin resistance related methyltransferase (e.g. ErmB or ErmC) via horizontal gene transfer. Next to post transcriptional RNA modification, mutation of the specific A (e.g. A→G, found also in eukaryotic 28S rRNA) renders bacteria resistant. Of note, both RNA alterations abrogated activation of TLR13, thereby enabling immune evasion.
Utilizing Tlr23479-/- mice, we observed Gram negative bacterial total RNA to be non TLR13 activating in contrast to purified Gram negative bacterial 23S rRNA. We speculate that it is another RNA subspecies that inhibits the stimulative capacity of 23S rRNA.
Keywords:
TLRs (Toll-like receptors),
bacteria recognition,
TLR13,
RNA recognition,
23S rRNA
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Innate immunity
Citation:
Krüger
A,
Oldenburg
M,
Ferstl
R,
Kaufmann
A,
Nees
G,
Buer
J,
Wagner
H,
Bauer
S,
Hochrein
H and
Kirschning
CJ
(2013). Bacterial 23S rRNA is recognized by the endosomal TLR13 unless it is modified to constitute erythromycin resistance.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.01144
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Received:
15 Jul 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Ms. Anne Krüger, University of Duisburg-Essen, Institute of Medical Microbiology, Essen, NRW, 45147, Germany, anne.krueger@uk-essen.de