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

 Previous Article  |  Next Article 

Infection and Immunity, April 2005, p. 2040-2050, Vol. 73, No. 4
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.4.2040-2050.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Impact of the SpeB Protease on Binding of the Complement Regulatory Proteins Factor H and Factor H-Like Protein 1 by Streptococcus pyogenes

Lin Wei, Vinod Pandiripally, Eugene Gregory, Micaya Clymer, and David Cue^*

Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas

Received 25 October 2004/ Returned for modification 18 November 2004/ Accepted 29 November 2004

Microbial pathogens often exploit human complement regulatory proteins such as factor H (FH) and factor H-like protein 1 (FHL-1) for immune evasion. Fba is an FH and FHL-1 binding protein expressed on the surface of the human pathogenic bacterium Streptococcus pyogenes, a common agent of pharyngeal, skin, and soft-tissue infections. Fba has been shown to contribute to phagocytosis resistance, intracellular invasion, and virulence in mice. Here, we look at the role of Fba in recruitment of FH and FHL-1 by five serotype M1 isolates of streptococci. Inactivation of fba greatly inhibited binding of FH and FHL-1 by all isolates, indicating that Fba is a major FH and FHL-1 binding factor of serotype M1 streptococci. For three isolates, FH binding was significantly reduced in stationary-phase cultures and correlated with high levels of protease activity and SpeB (an extracellular cysteine protease) protein in culture supernatants. Analysis of a speB mutant confirmed that SpeB accounts for the loss of Fba from the cell surface, suggesting that the protease may modulate FH and FHL-1 recruitment during infection. Comparisons of fba DNA sequences revealed that the FH and FHL-1 binding site in Fba is conserved among the M1 isolates. Although the ligand binding site is not strictly conserved in Fba from a serotype M49 isolate, the M49 Fba protein was found to bind both FH and FHL-1. Collectively, these data indicate that binding of FH and FHL-1 is a conserved function of Fba while modulation of Fba function by SpeB is variable.

Editor: J. T. Barbieri

Present address: Department of Immunology, Hebei Medical University, Shijiazhuang, China.

This article has been cited by other articles:

• Terao, Y., Mori, Y., Yamaguchi, M., Shimizu, Y., Ooe, K., Hamada, S., Kawabata, S. (2008). Group A Streptococcal Cysteine Protease Degrades C3 (C3b) and Contributes to Evasion of Innate Immunity. J. Biol. Chem. 283: 6253-6260 [Abstract] [Full Text]  
• Kuo, C.-F., Lin, Y.-S., Chuang, W.-J., Wu, J.-J., Tsao, N. (2008). Degradation of Complement 3 by Streptococcal Pyrogenic Exotoxin B Inhibits Complement Activation and Neutrophil Opsonophagocytosis. Infect. Immun. 76: 1163-1169 [Abstract] [Full Text]  
• Behnsen, J., Hartmann, A., Schmaler, J., Gehrke, A., Brakhage, A. A., Zipfel, P. F. (2008). The Opportunistic Human Pathogenic Fungus Aspergillus fumigatus Evades the Host Complement System. Infect. Immun. 76: 820-827 [Abstract] [Full Text]  
• Lizano, S., Luo, F., Bessen, D. E. (2007). Role of Streptococcal T Antigens in Superficial Skin Infection. J. Bacteriol. 189: 1426-1434 [Abstract] [Full Text]  
• Baums, C. G., Kaim, U., Fulde, M., Ramachandran, G., Goethe, R., Valentin-Weigand, P. (2006). Identification of a Novel Virulence Determinant with Serum Opacification Activity in Streptococcus suis.. Infect. Immun. 74: 6154-6162 [Abstract] [Full Text]