These authors contributed equally to this work.
Molecular architecture of Streptococcus pneumoniae surface thioredoxin-fold lipoproteins crucial for extracellular oxidative stress resistance and maintenance of virulence
Article first published online: 18 OCT 2013
© 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
EMBO Molecular Medicine
Volume 5, Issue 12, pages 1852–1870, December 2013
How to Cite
Saleh, M., Bartual, S. G., Abdullah, M. R., Jensch, I., Asmat, T. M., Petruschka, L., Pribyl, T., Gellert, M., Lillig, C. H., Antelmann, H., Hermoso, J. A. and Hammerschmidt, S. (2013), Molecular architecture of Streptococcus pneumoniae surface thioredoxin-fold lipoproteins crucial for extracellular oxidative stress resistance and maintenance of virulence. EMBO Mol Med, 5: 1852–1870. doi: 10.1002/emmm.201202435
See accompanying article 10.1002/emmm.201303482
- Issue published online: 2 DEC 2013
- Article first published online: 18 OCT 2013
- Manuscript Accepted: 10 SEP 2013
- Manuscript Revised: 15 AUG 2013
- Manuscript Received: 29 DEC 2012
- Deutsche Forschungsgemeinschaft. Grant Numbers: DFG HA3125/4-2, DFG AN746/3-1, BFU2011-25326, S2010/BMD-2457
- EU FP7 CAREPNEUMO. Grant Number: EU-CP223111
- oxidative stress;
The respiratory pathogen Streptococcus pneumoniae has evolved efficient mechanisms to resist oxidative stress conditions and to displace other bacteria in the nasopharynx. Here we characterize at physiological, functional and structural levels two novel surface-exposed thioredoxin-family lipoproteins, Etrx1 and Etrx2. The impact of both Etrx proteins and their redox partner methionine sulfoxide reductase SpMsrAB2 on pneumococcal pathogenesis was assessed in mouse virulence studies and phagocytosis assays. The results demonstrate that loss of function of either both Etrx proteins or SpMsrAB2 dramatically attenuated pneumococcal virulence in the acute mouse pneumonia model and that Etrx proteins compensate each other. The deficiency of Etrx proteins or SpMsrAB2 further enhanced bacterial uptake by macrophages, and accelerated pneumococcal killing by H2O2 or free methionine sulfoxides (MetSO). Moreover, the absence of both Etrx redox pathways provokes an accumulation of oxidized SpMsrAB2 in vivo. Taken together our results reveal insights into the role of two extracellular electron pathways required for reduction of SpMsrAB2 and surface-exposed MetSO. Identification of this system and its target proteins paves the way for the design of novel antimicrobials.