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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Glycolytic Inhibitors As Leads For Drug Discovery In The Pathogenic Free-Living Amoebae, Jillian Milanes
Glycolytic Inhibitors As Leads For Drug Discovery In The Pathogenic Free-Living Amoebae, Jillian Milanes
All Dissertations
The free-living amoeba, Naegleria fowleri, can cause a rare yet usually lethal infection of the brain called primary amebic meningoencephalitis. Because of poor diagnostics and limited treatment options, the mortality rate associated with the disease is >97%. Due to our finding that glucose is critical for trophozoite growth in culture, we have been interested in exploiting amoebae glucose metabolism to identify new potential drug targets. We have characterized the first enzyme of the glycolytic pathway, glucokinase (Glck), from N. fowleri and two other pathogenic free-living amoeba, Acanthamoeba castellanii and Balamuthia mandrillaris. We have assessed their biochemical properties and …
Cellulose Degradation: A Therapeutic Strategy In The Improved Treatment Of Acanthamoeba Infections, Sahreena Lakhundi, Ruqaiyyah Siddiqui, Naveed Ahmed Khan
Cellulose Degradation: A Therapeutic Strategy In The Improved Treatment Of Acanthamoeba Infections, Sahreena Lakhundi, Ruqaiyyah Siddiqui, Naveed Ahmed Khan
Department of Biological & Biomedical Sciences
Acanthamoeba is an opportunistic free-living amoeba that can cause blinding keratitis and fatal brain infection. Early diagnosis, followed by aggressive treatment is a pre-requisite in the successful treatment but even then the prognosis remains poor. A major drawback during the course of treatment is the ability of the amoeba to enclose itself within a shell (a process known as encystment), making it resistant to chemotherapeutic agents. As the cyst wall is partly made of cellulose, thus cellulose degradation offers a potential therapeutic strategy in the effective targeting of trophozoite encased within the cyst walls. Here, we present a comprehensive report …
Acanthamoeba Castellanii Of The T4 Genotype Is A Potential Environmental Host For Enterobacter Aerogenes And Aeromonas Hydrophila, Farzana Abubakar Yousuf, Ruqaiyyah Siddiqui, Naveed Ahmed Khan
Acanthamoeba Castellanii Of The T4 Genotype Is A Potential Environmental Host For Enterobacter Aerogenes And Aeromonas Hydrophila, Farzana Abubakar Yousuf, Ruqaiyyah Siddiqui, Naveed Ahmed Khan
Department of Biological & Biomedical Sciences
Background: Acanthamoeba can interact with a wide range of microorganisms such as viruses, algae, yeasts, protists and bacteria including Legionella pneumophila, Pseudomonas aeruginosa, Vibrio cholerae, Helicobacter pylori, Listeria monocytogenes, Mycobacterium spp., and Escherichia coli. In this capacity, Acanthamoeba has been suggested as a vector in the transmission of bacterial pathogens to the susceptible hosts.
Methods: Here, we used a keratitis isolate of A. castellanii of the T4 genotype and studied its interactions with two bacterial genera which have not been tested before, Enterobacter aerogenes, and Aeromonas hydrophila, as well as E. coli. Assays were performed to determine bacterial association with …
Photochemotherapeutic Strategies Against Acanthamoeba Keratitis, Ruqaiyyah Siddiqui, Naveed Ahmed Khan
Photochemotherapeutic Strategies Against Acanthamoeba Keratitis, Ruqaiyyah Siddiqui, Naveed Ahmed Khan
Department of Biological & Biomedical Sciences
Here, we determined the potential of photochemotherapy, namely the application of photodynamic compounds followed by exposure to a suitable source of UV-visible radiation against corneal pathogen, Acanthamoeba. Organometallic macromolecule, tin porphyrin [Sn(IV)porphyrin] was synthesized and purity confirmed using nuclear magnetic resonance spectroscopy. The Sn(IV)porphyrin was tested against a keratitis isolate of Acanthamoeba castellanii belonging to the T4 genotype using growth and viability assays. The effects of Sn(IV)porphyrin on A. castellanii binding to and cytopathogenicity of human corneal epithelial cells in vitro were tested. The metalloporphyrin showed potent amoebistatic effects. The tin porphyrin inhibited amoebae binding to and cytopathogenicity of corneal …
The Role Of Src Kinase In The Biology And Pathogenesis Of Acanthamoeba Castellanii, Ruqaiyyah Siddiqui, Junaid Iqbal, Marie-Josee Maugueret, Naveed Ahmed Khan
The Role Of Src Kinase In The Biology And Pathogenesis Of Acanthamoeba Castellanii, Ruqaiyyah Siddiqui, Junaid Iqbal, Marie-Josee Maugueret, Naveed Ahmed Khan
Department of Biological & Biomedical Sciences
Background: Acanthamoeba species are the causative agents of fatal granulomatous encephalitis in humans. Haematogenous spread is thought to be a primary step, followed by blood-brain barrier penetration, in the transmission of Acanthmaoeba into the central nervous system, but the associated molecular mechanisms remain unclear. Here, we evaluated the role of Src, a non-receptor protein tyrosine kinase in the biology and pathogenesis of Acanthamoeba.
Methods: Amoebistatic and amoebicidal assays were performed by incubating amoeba in the presence of Src kinase-selective inhibitor, PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine) and its inactive analog, PP3 (4-amino-7-phenylpyrazolo[3,4-d]pyrimidine). Using this inhibitor, the role of Src kinase in A. castellanii interactions …