This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lei, B.
Right arrow Articles by Musser, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lei, B.
Right arrow Articles by Musser, J. M.

 Previous Article  |  Next Article 

Infection and Immunity, August 2002, p. 4494-4500, Vol. 70, No. 8
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.8.4494-4500.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Identification and Characterization of a Novel Heme-Associated Cell Surface Protein Made by Streptococcus pyogenes

Benfang Lei,1 Laura M. Smoot,1 Heather M. Menning,1 Jovanka M. Voyich,1 Subbarao V. Kala,2 Frank R. Deleo,1 Sean D. Reid,1 and James M. Musser1*

Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840,1 Department of Pathology, Baylor College of Medicine, Houston, Texas 770302

Received 23 January 2002/ Returned for modification 28 February 2002/ Accepted 19 April 2002

Analysis of the genome sequence of a serotype M1 group A Streptococcus (GAS) strain identified a gene encoding a previously undescribed putative cell surface protein. The gene was cloned from a serotype M1 strain, and the recombinant protein was overexpressed in Escherichia coli and purified to homogeneity. The purified protein was associated with heme in a 1:1 stoichiometry. This streptococcal heme-associated protein, designated Shp, was produced in vitro by GAS, located on the bacterial cell surface, and accessible to specific antibody raised against the purified recombinant protein. Mice inoculated subcutaneously with GAS and humans with invasive infections and pharyngitis caused by GAS seroconverted to Shp, indicating that Shp was produced in vivo. The blood of mice actively immunized with Shp had significantly higher bactericidal activity than the blood of unimmunized mice. The shp gene was cotranscribed with eight contiguous genes, including homologues of an ABC transporter involved in iron uptake in gram-negative bacteria. Our results indicate that Shp is a novel cell surface heme-associated protein.

* Corresponding author. Mailing address: Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th St., Hamilton, MT 59840. Phone: (406) 363-9315. Fax: (406) 363-9427. E-mail: jmusser{at}niaid.nih.gov.

Editor: E. I. Tuomanen

Infection and Immunity, August 2002, p. 4494-4500, Vol. 70, No. 8
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.8.4494-4500.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Allen, C. E., Schmitt, M. P. (2009). HtaA Is an Iron-Regulated Hemin Binding Protein Involved in the Utilization of Heme Iron in Corynebacterium diphtheriae. J. Bacteriol. 191: 2638-2648 [Abstract] [Full Text]  
  • Fisher, M., Huang, Y.-S., Li, X., McIver, K. S., Toukoki, C., Eichenbaum, Z. (2008). Shr Is a Broad-Spectrum Surface Receptor That Contributes to Adherence and Virulence in Group A Streptococcus. Infect. Immun. 76: 5006-5015 [Abstract] [Full Text]  
  • Zhu, H., Xie, G., Liu, M., Olson, J. S., Fabian, M., Dooley, D. M., Lei, B. (2008). Pathway for Heme Uptake from Human Methemoglobin by the Iron-regulated Surface Determinants System of Staphylococcus aureus. J. Biol. Chem. 283: 18450-18460 [Abstract] [Full Text]  
  • Liu, M., Tanaka, W. N., Zhu, H., Xie, G., Dooley, D. M., Lei, B. (2008). Direct Hemin Transfer from IsdA to IsdC in the Iron-regulated Surface Determinant (Isd) Heme Acquisition System of Staphylococcus aureus. J. Biol. Chem. 283: 6668-6676 [Abstract] [Full Text]  
  • Ran, Y., Zhu, H., Liu, M., Fabian, M., Olson, J. S., Aranda, R. IV, Phillips, G. N. Jr., Dooley, D. M., Lei, B. (2007). Bis-methionine Ligation to Heme Iron in the Streptococcal Cell Surface Protein Shp Facilitates Rapid Hemin Transfer to HtsA of the HtsABC Transporter. J. Biol. Chem. 282: 31380-31388 [Abstract] [Full Text]  
  • Grigg, J. C., Vermeiren, C. L., Heinrichs, D. E., Murphy, M. E. P. (2007). Heme Coordination by Staphylococcus aureus IsdE. J. Biol. Chem. 282: 28815-28822 [Abstract] [Full Text]  
  • Liu, M., Zhu, H., Zhang, J., Lei, B. (2007). Active and Passive Immunizations with the Streptococcal Esterase Sse Protect Mice against Subcutaneous Infection with Group A Streptococci. Infect. Immun. 75: 3651-3657 [Abstract] [Full Text]  
  • Torres, V. J., Pishchany, G., Humayun, M., Schneewind, O., Skaar, E. P. (2006). Staphylococcus aureus IsdB Is a Hemoglobin Receptor Required for Heme Iron Utilization. J. Bacteriol. 188: 8421-8429 [Abstract] [Full Text]  
  • Hanks, T. S., Liu, M., McClure, M. J., Fukumura, M., Duffy, A., Lei, B. (2006). Differential Regulation of Iron- and Manganese-Specific MtsABC and Heme-Specific HtsABC Transporters by the Metalloregulator MtsR of Group A Streptococcus. Infect. Immun. 74: 5132-5139 [Abstract] [Full Text]  
  • Nygaard, T. K., Blouin, G. C., Liu, M., Fukumura, M., Olson, J. S., Fabian, M., Dooley, D. M., Lei, B. (2006). The Mechanism of Direct Heme Transfer from the Streptococcal Cell Surface Protein Shp to HtsA of the HtsABC Transporter. J. Biol. Chem. 281: 20761-20771 [Abstract] [Full Text]  
  • Skaar, E. P., Gaspar, A. H., Schneewind, O. (2006). Bacillus anthracis IsdG, a Heme-Degrading Monooxygenase. J. Bacteriol. 188: 1071-1080 [Abstract] [Full Text]  
  • Bates, C. S., Toukoki, C., Neely, M. N., Eichenbaum, Z. (2005). Characterization of MtsR, a New Metal Regulator in Group A Streptococcus, Involved in Iron Acquisition and Virulence. Infect. Immun. 73: 5743-5753 [Abstract] [Full Text]  
  • Liu, M., Lei, B. (2005). Heme Transfer from Streptococcal Cell Surface Protein Shp to HtsA of Transporter HtsABC. Infect. Immun. 73: 5086-5092 [Abstract] [Full Text]  
  • Graham, M. R., Virtaneva, K., Porcella, S. F., Barry, W. T., Gowen, B. B., Johnson, C. R., Wright, F. A., Musser, J. M. (2005). Group A Streptococcus Transcriptome Dynamics during Growth in Human Blood Reveals Bacterial Adaptive and Survival Strategies. Am. J. Pathol. 166: 455-465 [Abstract] [Full Text]  
  • Skaar, E. P., Gaspar, A. H., Schneewind, O. (2004). IsdG and IsdI, Heme-degrading Enzymes in the Cytoplasm of Staphylococcus aureus. J. Biol. Chem. 279: 436-443 [Abstract] [Full Text]  
  • Kunkle, C. A., Schmitt, M. P. (2003). Analysis of the Corynebacterium diphtheriae DtxR Regulon: Identification of a Putative Siderophore Synthesis and Transport System That Is Similar to the Yersinia High-Pathogenicity Island-Encoded Yersiniabactin Synthesis and Uptake System. J. Bacteriol. 185: 6826-6840 [Abstract] [Full Text]  
  • Lei, B., Liu, M., Voyich, J. M., Prater, C. I., Kala, S. V., DeLeo, F. R., Musser, J. M. (2003). Identification and Characterization of HtsA, a Second Heme-Binding Protein Made by Streptococcus pyogenes. Infect. Immun. 71: 5962-5969 [Abstract] [Full Text]  
  • Janulczyk, R., Ricci, S., Bjorck, L. (2003). MtsABC Is Important for Manganese and Iron Transport, Oxidative Stress Resistance, and Virulence of Streptococcus pyogenes. Infect. Immun. 71: 2656-2664 [Abstract] [Full Text]  
  • Smoot, L. M., McCormick, J. K., Smoot, J. C., Hoe, N. P., Strickland, I., Cole, R. L., Barbian, K. D., Earhart, C. A., Ohlendorf, D. H., Veasy, L. G., Hill, H. R., Leung, D. Y. M., Schlievert, P. M., Musser, J. M. (2002). Characterization of Two Novel Pyrogenic Toxin Superantigens Made by an Acute Rheumatic Fever Clone of Streptococcus pyogenes Associated with Multiple Disease Outbreaks. Infect. Immun. 70: 7095-7104 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»