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
Google Scholar
Right arrow Articles by Kenedy, M. R.
Right arrow Articles by Akins, D. R.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kenedy, M. R.
Right arrow Articles by Akins, D. R.

 Previous Article  |  Next Article 

Infection and Immunity, July 2009, p. 2773-2782, Vol. 77, No. 7
0019-9567/09/$08.00+0     doi:10.1128/IAI.00318-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

CspA-Mediated Binding of Human Factor H Inhibits Complement Deposition and Confers Serum Resistance in Borrelia burgdorferi{triangledown}

Melisha R. Kenedy,1 Santosh R. Vuppala,1 Corinna Siegel,2 Peter Kraiczy,2 and Darrin R. Akins1*

Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104,1 Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Frankfurt, Germany D-605962

Received 19 March 2009/ Returned for modification 29 April 2009/ Accepted 4 May 2009

Borrelia burgdorferi has developed efficient mechanisms for evading the innate immune response during mammalian infection and has been shown to be resistant to the complement-mediated bactericidal activity of human serum. It is well recognized that B. burgdorferi expresses multiple lipoproteins on its surface that bind the human complement inhibitors factor H and factor H-like protein 1 (FH/FHL-1). The binding of FH/FHL-1 on the surface of B. burgdorferi is thought to enhance its ability to evade serum-mediated killing during the acute phase of infection. One of the key B. burgdorferi FH/FHL-1 binding proteins identified thus far was designated CspA. While it is known that CspA binds FH/FHL-1, it is unclear how the interaction between CspA and FH/FHL-1 specifically enhances serum resistance. To better understand how CspA mediates serum resistance in B. burgdorferi, we inactivated cspA in a virulent strain of B. burgdorferi. An affinity ligand blot immunoassay and indirect immunofluorescence revealed that the CspA mutant does not efficiently bind human FH to its surface. Consistent with the lack of FH binding, the CspA mutant was also highly sensitive to killing by human serum. Additionally, the deposition of complement components C3, C6, and C5b-9 was enhanced on the surface of the CspA mutant compared to that of the wild-type strain. The combined data lead us to conclude that the CspA-mediated binding of human FH confers serum resistance by directly inhibiting complement deposition on the surface of B. burgdorferi.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104. Phone: (405) 271-2133, ext. 46640. Fax: (405) 271-3117. E-mail: darrin-akins{at}ouhsc.edu

{triangledown} Published ahead of print on 18 May 2009.

Editor: J. B. Bliska

Infection and Immunity, July 2009, p. 2773-2782, Vol. 77, No. 7
0019-9567/09/$08.00+0     doi:10.1128/IAI.00318-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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