Browsing by Subject "Protozoan antigens"

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    Azurin-Like Protein Blocks Invasion of Toxoplasma gondii through Potential Interactions with Parasite Surface Antigen SAG1
    (American Society for Microbiology, 2008) Naguleswaran, Arunasalam; Fialho, Arsenio M.; Chaudhari, Anita; Hong, Chang Soo; Chakrabarty, Ananda M.; Sullivan, William J., Jr.; Pharmacology and Toxicology, School of Medicine
    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.
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    Improving the diagnosis of severe malaria in African children using platelet counts and plasma PfHRP2 concentrations
    (American Association for the Advancement of Science, 2022) Watson, James A.; Uyoga, Sophie; Wanjiku, Perpetual; Makale, Johnstone; Nyutu, Gideon M.; Mturi, Neema; George, Elizabeth C.; Woodrow, Charles J.; Day, Nicholas P. J.; Bejon, Philip; Opoka, Robert O.; Dondorp, Arjen M.; John, Chandy C.; Maitland, Kathryn; Williams, Thomas N.; White, Nicholas J.; Pediatrics, School of Medicine
    Severe malaria caused by Plasmodium falciparum is difficult to diagnose accurately in children in high-transmission settings. Using data from 2649 pediatric and adult patients enrolled in four studies of severe illness in three countries (Bangladesh, Kenya, and Uganda), we fitted Bayesian latent class models using two diagnostic markers: the platelet count and the plasma concentration of P. falciparum histidine-rich protein 2 (PfHRP2). In severely ill patients with clinical features consistent with severe malaria, the combination of a platelet count of ≤150,000/μl and a plasma PfHRP2 concentration of ≥1000 ng/ml had an estimated sensitivity of 74% and specificity of 93% in identifying severe falciparum malaria. Compared with misdiagnosed children, pediatric patients with true severe malaria had higher parasite densities, lower hematocrits, lower rates of invasive bacterial disease, and a lower prevalence of both sickle cell trait and sickle cell anemia. We estimate that one-third of the children enrolled into clinical studies of severe malaria in high-transmission settings in Africa had another cause of their severe illness.