Bacillus anthracis protease InhA increases blood-brain barrier permeability and contributes to cerebral hemorrhages
| Autor: | Charles L. Bailey, Taissia G. Popova, Jessica H. Tonry, Kwang Sik Kim, Nalini Ramarao, Myung Chul Chung, Serguei G. Popov, Dhritiman V. Mukherjee |
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| Přispěvatelé: | George Mason University, Johns Hopkins University (JHU), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, U.S. Department of Defense [DAMD 17-03-C-01220], U.S. Department of Energy [DE-FC52-FC04NA25455] |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Bacterial Diseases
Cytoplasm Mouse LUNG EPITHELIAL-CELLS [SDV]Life Sciences [q-bio] lcsh:Medicine Pathogenesis ACTIVATION Mice chemistry.chemical_compound Infectious Diseases of the Nervous System INFECTION Electric Impedance lcsh:Science Evans Blue 0303 health sciences Metalloproteinase Multidisciplinary biology Tight junction INHA Animal Models Extravasation Bacterial Pathogens 3. Good health Bacillus anthracis Host-Pathogen Interaction Infectious Diseases medicine.anatomical_structure Neurology Blood-Brain Barrier Medicine Female ZONULA OCCLUDENS-1 Nanospheres Research Article EXPRESSION Blotting Western ENDOTHELIAL-CELLS INHALATIONAL ANTHRAX TOXIN METALLOPROTEASES PATHOLOGY Blood–brain barrier Microbiology Permeability Anthrax 03 medical and health sciences Model Organisms Bacterial Proteins Bacterial Meningitis medicine Animals Humans Biology Cerebral Hemorrhage 030304 developmental biology Gram Positive 030306 microbiology lcsh:R Endothelial Cells Membrane Proteins Phosphoproteins biology.organism_classification Emerging Infectious Diseases chemistry Zonula Occludens-1 Protein Mutant Proteins lcsh:Q |
| Zdroj: | PLoS ONE, Vol 6, Iss 3, p e17921 (2011) PLoS ONE PLoS ONE, Public Library of Science, 2011, 6 (3), ⟨10.1371/journal.pone.0017921⟩ Plos One 3 (6), . (2011) |
| ISSN: | 1932-6203 |
| Popis: | International audience; Hemorrhagic meningitis is a fatal complication of anthrax, but its pathogenesis remains poorly understood. The present study examined the role of B. anthracis-secreted metalloprotease InhA on monolayer integrity and permeability of human brain microvasculature endothelial cells (HBMECs) which constitute the blood-brain barrier (BBB). Treatment of HBMECs with purified InhA resulted in a time-dependent decrease in trans-endothelial electrical resistance (TEER) accompanied by zonula occluden-1 (ZO-1) degradation. An InhA-expressing B. subtilis exhibited increased permeability of HBMECs, which did not occur with the isogenic inhA deletion mutant (Delta inhA) of B. anthracis, compared with the corresponding wild-type strain. Mice intravenously administered with purified InhA or nanoparticles-conjugated to InhA demonstrated a time-dependent Evans Blue dye extravasation, leptomeningeal thickening, leukocyte infiltration, and brain parenchymal distribution of InhA indicating BBB leakage and cerebral hemorrhage. Mice challenged with vegetative bacteria of the Delta inhA strain of B. anthracis exhibited a significant decrease in leptomeningeal thickening compared to the wildtype strain. Cumulatively, these findings indicate that InhA contributes to BBB disruption associated with anthrax meningitis through proteolytic attack on the endothelial tight junctional protein zonula occluden (ZO)-1. |
| Databáze: | OpenAIRE |
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