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Cd147 as receptor for pilus-mediated adhesion of meningococci to vascular endothelia

a technology of cd147 and pilus, which is applied in the direction of peptides, biological material analysis, dna/rna fragmentation, etc., can solve the problems of difficult identification of molecular determinants involved in direct interaction with host cell receptors using a genetic approach, and achieve the effects of preventing primary attachment of meningococci, preventing bacterial meningitis and/or purpura fulminans, and preventing meningeal

Inactive Publication Date: 2018-11-29
INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM) +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The invention is about finding a way to stop meningococci (a type of bacteria) from sticking to the surface of host cells and causing infections. This is done by blocking the interaction between specific proteins on the meningococci and the host cells. The patent also includes a step where the two proteins come close enough to each other to transfer energy between them. This blockage technique could be used to develop new treatments for meningococcal infections.

Problems solved by technology

The adhesive properties of type IV pili are also modulated by components of the pilus machinery such as the PilC1 allele, making it difficult to identify the molecular determinants involved in direct interaction with host cell receptors using a genetic approach.

Method used

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  • Cd147 as receptor for pilus-mediated adhesion of meningococci to vascular endothelia
  • Cd147 as receptor for pilus-mediated adhesion of meningococci to vascular endothelia
  • Cd147 as receptor for pilus-mediated adhesion of meningococci to vascular endothelia

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Experimental program
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Embodiment Construction

Material and Methods

Serial Analysis of Gene Expression Adapted for Downsized Extracts (SADE).

[0271]200 μg of RNA extracted from 2×107 untreated or TPA treated BB19 cells 16 hours after treatment with TPA, was used as a substrate for SADE. The SADE screen was carried out as described in Virlon et al., 1999, Proc Natl Acad Sci USA, 96:15286-15291. Briefly, total RNA was extracted from cells, poly-adenylated RNA was selected on oligo-dT columns and tagged cDNA was synthesized from the poly-A RNAs. Concatemers of DNA tags were sequenced and the number of sequenced tags differentially represented in the two libraries was determined and analysed using Monte Carlo statistical analysis.

Antibodies and Reagents

[0272]Anti-hCD147 antibodies were purchased from AbD Serotec, anti-hCD44 mAb from Immunotech, antihlCAM-1 from R&D Systems, anti-GFAP and anti-vimentin from Sigma Aldrich. Polyclonal antiserum raised against ezrin was obtained from P. Mangeat (CNRS UMR 5539, Montpelier, France). mAb rai...

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Abstract

The present invention concerns the use of an inhibitor of an interaction between type IV pilus-associated protein and CD147 for preventing or treating meningoccal bacteraemia and / or infection. The present invention also relates to the combined use of such inhibitor and of an anti-bacterial compound, such as one used to prevent or treat a meningococcal infection. The invention also relates to a method for the prevention and / or treatment of meningococcal bacteraemia and / or infection, and to a method for screening inhibitors of the interaction between type IV pilus-associated protein and CD147.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a divisional application of U.S. Ser. No. 14 / 405,444, having a filing date of Dec. 4, 2014, which was a 371 application of International application PCT / EP2013 / 064900 filed on Jul. 15, 2013, which claimed the benefit of European patent application 12305920.6, filed Jul. 27, 2012, all of said applications incorporated herein by reference.FIELD OF THE INVENTION[0002]The present invention concerns the use of an inhibitor of an interaction between type IV pilus-associated protein and CD147 for preventing or treating meningococcal bacteraemia and / or infection. The present invention also relates to the combined use of such inhibitor and of an anti-bacterial compound, such as one used to prevent or treat a meningococcal infection. The invention also relates to a method for the prevention and / or treatment of meningococcal bacteraemia and / or infection, and to a method for screening inhibitors of the interaction between type IV ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C07K14/705C12N15/113A61K39/395A61K39/40
CPCC12N15/1138C07K14/70503A61K39/3955A61K39/40A61K2039/505C07K14/22G01N2500/10C12N2310/11G01N33/5041G01N2333/195G01N2333/70596G01N2500/02C07K2317/76C07K16/2803C07K2319/32C07K2319/30C07K14/70596A61K39/095A61P31/04
Inventor NASSIF, XAVIERBOURDOULOUS, SANDRINEJOIN-LAMBERT, OLIVIER
Owner INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM)
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