11 research outputs found

    Diphtheria Toxin and Cytosolic Translocation Factors

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    Streptococcus Pneumoniae Intracranial Abscess and Post-Infectious Vasculitis

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    Intracranial abscesses are rare complications of Streptococcus pneumoniae infections, and to our knowledge, there have been no case reports of post-infectious vasculitis developing in such patients. Here we describe the case of a 48-year-old post-splenectomy male who developed post-infectious vasculitis following S. pneumoniae otitis media complicated by mastoiditis, osteomyelitis, meningitis, and intracranial abscess. Clinicians ought to be aware of the possible adverse outcomes of invasive S. pneumoniae and the limitations of current treatment options

    The cytosolic entry of diphtheria toxin catalytic domain requires a host cell cytosolic translocation factor complex

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    In vitro delivery of the diphtheria toxin catalytic (C) domain from the lumen of purified early endosomes to the external milieu requires the addition of both ATP and a cytosolic translocation factor (CTF) complex. Using the translocation of C-domain ADP-ribosyltransferase activity across the endosomal membrane as an assay, the CTF complex activity was 650–800-fold purified from human T cell and yeast extracts, respectively. The chaperonin heat shock protein (Hsp) 90 and thioredoxin reductase were identified by mass spectrometry sequencing in CTF complexes purified from both human T cell and yeast. Further analysis of the role played by these two proteins with specific inhibitors, both in the in vitro translocation assay and in intact cell toxicity assays, has demonstrated their essential role in the productive delivery of the C-domain from the lumen of early endosomes to the external milieu. These results confirm and extend earlier observations of diphtheria toxin C-domain unfolding and refolding that must occur before and after vesicle membrane translocation. In addition, results presented here demonstrate that thioredoxin reductase activity plays an essential role in the cytosolic release of the C-domain. Because analogous CTF complexes have been partially purified from mammalian and yeast cell extracts, results presented here suggest a common and fundamental mechanism for C-domain translocation across early endosomal membranes

    Streptococcus pneumoniae intracranial abscess and post-infectious vasculitis

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    Intracranial abscesses are rare complications of <em>Streptococcus</em> <em>pneumoniae</em> infections, and to our knowledge, there have been no case reports of post-infectious vasculitis developing in such patients. Here we describe the case of a 48-year-old post-splenectomy male who developed post-infectious vasculitis following <em>S. pneumoniae</em> otitis media complicated by mastoiditis, osteomyelitis, meningitis, and intracranial abscess. Clinicians ought to be aware of the possible adverse outcomes of invasive <em>S. pneumoniae</em> and the limitations of current treatment options

    Post-COVID Kawasaki-like Multisystem Inflammatory Syndrome Complicated by Herpes Simplex Virus-1 in a Two-Year-Old Child

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    Multisystem inflammatory syndrome in children (MIS-C) is a rare, systemic inflammation following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We report a case of a 2-year-old male who presented with an exanthem and aberrant laboratory markers, mimicking Kawasaki disease but failing to meet the full diagnostic criteria. His course was further complicated by herpes Simplex Virus-1 (HSV-1) stomatitis
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