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 Google Scholar
Google Scholar
Right arrow Articles by Noto, J. M.
Right arrow Articles by Cornelissen, C. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Noto, J. M.
Right arrow Articles by Cornelissen, C. N.

 Previous Article  |  Next Article 

Infection and Immunity, May 2008, p. 1960-1969, Vol. 76, No. 5
0019-9567/08/$08.00+0     doi:10.1128/IAI.00020-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Identification of TbpA Residues Required for Transferrin-Iron Utilization by Neisseria gonorrhoeae{triangledown}

Jennifer M. Noto and Cynthia Nau Cornelissen*

Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298-0678

Received 7 January 2008/ Returned for modification 15 February 2008/ Accepted 6 March 2008

Neisseria gonorrhoeae requires iron for survival in the human host and therefore expresses high-affinity receptors for iron acquisition from host iron-binding proteins. The gonococcal transferrin-iron uptake system is composed of two transferrin binding proteins, TbpA and TbpB. TbpA is a TonB-dependent, outer membrane transporter critical for iron acquisition, while TbpB is a surface-exposed lipoprotein that increases the efficiency of iron uptake. The precise mechanism by which TbpA mediates iron acquisition has not been elucidated; however, the process is distinct from those of characterized siderophore transporters. Similar to these TonB-dependent transporters, TbpA is proposed to have two distinct domains, a β-barrel and a plug domain. We hypothesize that the TbpA plug coordinates iron and therefore potentially functions in multiple steps of transferrin-mediated iron acquisition. To test this hypothesis, we targeted a conserved motif within the TbpA plug domain and generated single, double, and triple alanine substitution mutants. Mutagenized TbpAs were expressed on the gonococcal cell surface and maintained wild-type transferrin binding affinity. Single alanine substitution mutants internalized iron at wild-type levels, while the double and triple mutants showed a significant decrease in iron uptake. Moreover, the triple alanine substitution mutant was unable to grow on transferrin as a sole iron source; however, expression of TbpB compensated for this defect. These data indicate that the conserved motif between residues 120 and 122 of the TbpA plug domain is critical for transferrin-iron utilization, suggesting that this region plays a role in iron acquisition that is shared by both TbpA and TbpB.

* Corresponding author. Mailing address: P.O. Box 980678, Richmond, VA 23298-0678. Phone: (804) 827-1754. Fax: (804) 828-9946. E-mail: cncornel{at}vcu.edu

{triangledown} Published ahead of print on 17 March 2008.

Editor: J. N. Weiser

Infection and Immunity, May 2008, p. 1960-1969, Vol. 76, No. 5
0019-9567/08/$08.00+0     doi:10.1128/IAI.00020-08
Copyright © 2008, 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»