Bacillus anthracis protease InhA increases blood-brain barrier permeability and contributes to cerebral hemorrhages.
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 consti...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3060093?pdf=render |
| _version_ | 1818319794267488256 |
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| author | Dhritiman V Mukherjee Jessica H Tonry Kwang Sik Kim Nalini Ramarao Taissia G Popova Charles Bailey Serguei Popov Myung-Chul Chung |
| author_facet | Dhritiman V Mukherjee Jessica H Tonry Kwang Sik Kim Nalini Ramarao Taissia G Popova Charles Bailey Serguei Popov Myung-Chul Chung |
| author_sort | Dhritiman V Mukherjee |
| collection | DOAJ |
| description | 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 (ΔinhA) 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 ΔinhA 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. |
| first_indexed | 2024-12-13T10:14:46Z |
| format | Article |
| id | doaj.art-f06923c9ce984243a84a924b53c41818 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T10:14:46Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f06923c9ce984243a84a924b53c418182022-12-21T23:51:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0163e1792110.1371/journal.pone.0017921Bacillus anthracis protease InhA increases blood-brain barrier permeability and contributes to cerebral hemorrhages.Dhritiman V MukherjeeJessica H TonryKwang Sik KimNalini RamaraoTaissia G PopovaCharles BaileySerguei PopovMyung-Chul ChungHemorrhagic 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 (ΔinhA) 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 ΔinhA 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.http://europepmc.org/articles/PMC3060093?pdf=render |
| spellingShingle | Dhritiman V Mukherjee Jessica H Tonry Kwang Sik Kim Nalini Ramarao Taissia G Popova Charles Bailey Serguei Popov Myung-Chul Chung Bacillus anthracis protease InhA increases blood-brain barrier permeability and contributes to cerebral hemorrhages. PLoS ONE |
| title | Bacillus anthracis protease InhA increases blood-brain barrier permeability and contributes to cerebral hemorrhages. |
| title_full | Bacillus anthracis protease InhA increases blood-brain barrier permeability and contributes to cerebral hemorrhages. |
| title_fullStr | Bacillus anthracis protease InhA increases blood-brain barrier permeability and contributes to cerebral hemorrhages. |
| title_full_unstemmed | Bacillus anthracis protease InhA increases blood-brain barrier permeability and contributes to cerebral hemorrhages. |
| title_short | Bacillus anthracis protease InhA increases blood-brain barrier permeability and contributes to cerebral hemorrhages. |
| title_sort | bacillus anthracis protease inha increases blood brain barrier permeability and contributes to cerebral hemorrhages |
| url | http://europepmc.org/articles/PMC3060093?pdf=render |
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