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Angiotensin II Receptor Type 1—A Novel Target for Preventing Neonatal Meningitis in Mice by Escherichia coli K1

Krishnan, Subramanian and Shanmuganathan, Muthusamy V. and Behenna, Douglas and Stoltz, Brian M. and Prasadarao, Nemani V. (2014) Angiotensin II Receptor Type 1—A Novel Target for Preventing Neonatal Meningitis in Mice by Escherichia coli K1. Journal of Infectious Diseases, 209 (3). pp. 409-419. ISSN 0022-1899. PMCID PMC3883175. https://resolver.caltech.edu/CaltechAUTHORS:20140214-093051277

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Abstract

The increasing incidence of Escherichia coli K1 meningitis due to escalating antibiotic resistance warrants alternate treatment options to prevent this deadly disease. We screened a library of small molecules from the National Institutes of Health clinical collection and identified telmisartan, an angiotensin II receptor type 1 (AT1R) blocker, as a potent inhibitor of E. coli invasion into human brain microvascular endothelial cells (HBMECs). Immunoprecipitation studies revealed that AT1R associates with endothelial cell gp96, the receptor in HBMECs for E. coli outer membrane protein A. HBMECs pretreated with telmisartan or transfected with AT1R small interfering RNA were resistant to E. coli invasion because of downregulation of protein kinase C-α phosphorylation. Administration of a soluble derivative of telmisartan to newborn mice before infection with E. coli prevented the onset of meningitis and suppressed neutrophil infiltration and glial cell migration in the brain. Therefore, telmisartan has potential as an alternate treatment option for preventing E. coli meningitis.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1093/infdis/jit499DOIArticle
http://jid.oxfordjournals.org/content/209/3/409PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883175/PubMed CentralArticle
ORCID:
AuthorORCID
Krishnan, Subramanian0000-0001-5780-7452
Stoltz, Brian M.0000-0001-9837-1528
Additional Information:© The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. Received 30 May 2013; accepted 13 August 2013; electronically published 16 September 2013. This work was supported by the National Institutes of Health (grants AI40567 and NS73115 to N. V. P.).
Funders:
Funding AgencyGrant Number
NIHAI40567
NIHNS73115
Subject Keywords:Angiotensin II receptor type I; protein kinase C-α; human brain endothelial cells; small molecules; brain; invasion; Escherichia coli K1
Issue or Number:3
PubMed Central ID:PMC3883175
Record Number:CaltechAUTHORS:20140214-093051277
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20140214-093051277
Official Citation:Krishnan, S., Shanmuganathan, M. V., Behenna, D., Stoltz, B. M., & Prasadarao, N. V. (2014). Angiotensin II Receptor Type 1—A Novel Target for Preventing Neonatal Meningitis in Mice by Escherichia coli K1. Journal of Infectious Diseases, 209(3), 409-419. doi: 10.1093/infdis/jit499
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:43829
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:18 Feb 2014 17:32
Last Modified:03 Oct 2019 06:11

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