Azurin-like protein blocks invasion of Toxoplasma gondii through potential interactions with parasite surface antigen SAG1.

Abstract

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.

• Authors: Arunasalam Naguleswaran, Arsenio M Fialho, Anita Chaudhari, Chang Soo Hong, Ananda M Chakrabarty, William J Sullivan Jr
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 52 Issue 2 Pg. 402-8 (Feb 2008) ISSN: 0066-4804 [Print] United States
• PMID: 18070964 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Protozoan
• Protozoan Proteins
• SAG1 antigen, Toxoplasma
• Azurin

Topics

• Amino Acid Sequence
• Animals
• Antigens, Protozoan (chemistry, genetics, metabolism)
• Azurin (chemistry, metabolism, pharmacology)
• Cell Adhesion
• Chlorocebus aethiops
• Fibroblasts
• Humans
• Models, Molecular
• Neisseria gonorrhoeae (metabolism)
• Neisseria meningitidis (metabolism)
• Protein Binding
• Protozoan Proteins (chemistry, genetics, metabolism)
• Surface Plasmon Resonance
• Toxoplasma (drug effects, genetics, pathogenicity)
• Vero Cells