Antimicrob Agents Chemother. 2007 Dec 10 [Epub ahead of print]
Azurin-like protein blocks invasion of Toxoplasma gondii through potential interactions with parasite surface antigen SAG1
Naguleswaran A, Fialho AM, Chaudhari A, Hong CS, Chakrabarty AM, Sullivan WJ Jr
Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, Indiana; Department of Microbiology & Immunology, University of Illinois College of Medicine, Chicago, Illinois; Institute for Biotechnology and Bioengineering (IBB), Centre for Biological and Chemical Engineering, Instituto Superior Tecnico, Lisbon, Portugal.
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 human AIDS virus HIV-1 and the protozoan parasite Plasmodium falciparum (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 with 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 are worthy of further study for development into potential therapeutic agents.
PMID: 18070964 [PubMed - as supplied by publisher]