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

Arunasalam Naguleswaran, Arsenio M. Fialho, Anita Chaudhari, Soo Hong Chang, Ananda M. Chakrabarty, William Sullivan

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)402-408
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume52
Issue number2
DOIs
StatePublished - Feb 2008

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Azurin
Toxoplasma
Surface Antigens
Parasites
Proteins
Host-Pathogen Interactions
Neisseria meningitidis
Surface Plasmon Resonance
Neisseria gonorrhoeae
Opportunistic Infections
Plasmodium falciparum
Pseudomonas aeruginosa
Malaria
HIV-1
Monoclonal Antibodies
HIV
Bacteria

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Azurin-like protein blocks invasion of Toxoplasma gondii through potential interactions with parasite surface antigen SAG1. / Naguleswaran, Arunasalam; Fialho, Arsenio M.; Chaudhari, Anita; Chang, Soo Hong; Chakrabarty, Ananda M.; Sullivan, William.

In: Antimicrobial Agents and Chemotherapy, Vol. 52, No. 2, 02.2008, p. 402-408.

Research output: Contribution to journalArticle

Naguleswaran, Arunasalam ; Fialho, Arsenio M. ; Chaudhari, Anita ; Chang, Soo Hong ; Chakrabarty, Ananda M. ; Sullivan, William. / Azurin-like protein blocks invasion of Toxoplasma gondii through potential interactions with parasite surface antigen SAG1. In: Antimicrobial Agents and Chemotherapy. 2008 ; Vol. 52, No. 2. pp. 402-408.
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