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 Naguleswaran, A.
Right arrow Articles by Sullivan, W. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Naguleswaran, A.
Right arrow Articles by Sullivan, W. J., Jr.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, February 2008, p. 402-408, Vol. 52, No. 2
0066-4804/08/$08.00+0     doi:10.1128/AAC.01005-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Azurin-Like Protein Blocks Invasion of Toxoplasma gondii through Potential Interactions with Parasite Surface Antigen SAG1{triangledown}

Arunasalam Naguleswaran,1 Arsenio M. Fialho,2,3 Anita Chaudhari,2 Chang Soo Hong,2 Ananda M. Chakrabarty,2 and William J. Sullivan Jr.1*

Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, Indiana,1 Department of Microbiology & Immunology, University of Illinois College of Medicine, Chicago, Illinois,2 Institute for Biotechnology and Bioengineering (IBB), Centre for Biological and Chemical Engineering, Instituto Superior Tecnico, Lisbon, Portugal3

Received 30 July 2007/ Returned for modification 28 August 2007/ Accepted 26 November 2007

Some pathogenic bacteria produce factors that have evolved a capacity to neutralize competing microbes. The cupredoxin family protein azurin, produced by Pseudomonas aeruginosa, exhibits a remarkable ability to impede invasion of a number of diverse intracellular pathogens, including the human AIDS virus human immunodeficiency virus type 1 and the protozoan parasite Plasmodium falciparum (which causes malaria). Here we report that azurin and an azurin-like protein (Laz) from gonococci/meningococci have activity against Toxoplasma, an apicomplexan parasite that causes opportunistic infection in immunocompromised individuals. We demonstrate that the mechanism of action for Laz involves interfering with the ability of Toxoplasma to adhere to host cells. Computer structural analysis reveals that azurin shares structural features with the predominant surface antigen SAG1, which is known to play an important role in parasite attachment. Interestingly, azurin also has structural similarities to a monoclonal antibody to SAG1. Surface plasmon resonance binding studies validate that SAG1 interacts strongly with Laz and, to lesser extent, azurin. Moreover, Toxoplasma mutants lacking SAG1 are not as susceptible to the growth-inhibitory effects of Laz. Collectively, our data show that Toxoplasma adhesion can be significantly impaired by Laz, and to some extent by azurin, via interactions with SAG1. These observations indicate that Laz can serve as an important tool in the study of host-pathogen interactions and is worthy of further study for development into potential therapeutic agents.

* Corresponding author. Mailing address: Pharmacology & Toxicology, Center for AIDS Research, Indiana University School of Medicine, 635 Barnhill Drive, MS A-525, Indianapolis, IN 46202. Phone: (317) 274-1573. Fax: (317) 274-7714. E-mail: wjsulliv{at}iupui.edu

{triangledown} Published ahead of print on 10 December 2007.

Antimicrobial Agents and Chemotherapy, February 2008, p. 402-408, Vol. 52, No. 2
0066-4804/08/$08.00+0     doi:10.1128/AAC.01005-07
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»