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Infection and Immunity, June 2008, p. 2612-2619, Vol. 76, No. 6
0019-9567/08/$08.00+0     doi:10.1128/IAI.00239-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The Signal Recognition Particle Pathway Is Required for Virulence in Streptococcus pyogenes

Jason W. Rosch ,^1,,¶ Luis Alberto Vega,^1, John M. Beyer,^1, Ada Lin,² and Michael G. Caparon^1*

Department of Molecular Microbiology, Washington University School of Medicine, Box 8230, St. Louis, Missouri 63110-1093,¹ Department of Pediatrics, Washington University School of Medicine, Box 8208, St. Louis, Missouri 63110-1093²

Received 13 February 2007/ Returned for modification 21 March 2007/ Accepted 1 April 2008

The signal recognition particle (SRP) pathway is a universally conserved pathway for targeting polypeptides for secretion via the cotranslational pathway. In particular, the SRP pathway is thought to be the main mechanism for targeting polypeptides in gram-positive bacteria, including a number of important human pathogens. Though widely considered to be an essential cellular component, recent advances have indicated this pathway may be dispensable in gram-positive bacteria of the genus Streptococcus under in vitro conditions. However, its importance for the pathogenesis of streptococcal disease is unknown. In this study, we investigated the importance of the SRP pathway for virulence factor secretion in the human pathogen Streptococcus pyogenes. While the SRP pathway was not found to be essential for viability in vitro, SRP mutants demonstrated a medium-specific growth defect that could be rescued by the addition of glucose. We also observed that a distinct subset of virulence factors were dependent upon the SRP pathway for secretion, whereas others were completely independent of this pathway. Significantly, deletion of the SRP pathway resulted in mutants that were highly attenuated in both a zebrafish model of necrotic myositis and a murine subcutaneous ulcer model, highlighting the importance of this pathway in vivo. These studies emphasize the importance of the SRP pathway for the in vivo survival and pathogenesis of S. pyogenes.

Published ahead of print on 14 April 2008.

Editor: F. C. Fang

These authors contributed equally to this work.

^¶ Present address: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105.

Present address: Indiana University School of Law, 211 South Indiana Ave., Bloomington, IN 47405-7001.