Avid Bioservices Inc (CDMO)

[biopharm]

October 11, 2019

A Chlamydia pneumoniae adhesin induces phosphatidylserine exposure on host cells

Oct 11, 2019

Jan N. Galle, Tim Fechtner, Thorsten Eierhoff, Winfried Römer & Johannes H. Hegemann


Abstract
In mammalian cells, the internal and external leaflets of the plasma membrane (PM) possess different phospholipids. Phosphatidylserine (PS) is normally confined to the inner (cytoplasmic) membrane leaflet. Here we report that the adhesin CPn0473 of the human pathogenic bacterium Chlamydia pneumoniae (Cpn) binds to the PM of human cells and induces PS externalization but unexpectedly not apoptosis. PS externalization is increased in human cells exposed to infectious Cpn cells expressing increased CPn0473 and reduced in exposure to Cpn expressing decreased CPn0473. CPn0473 binds specifically to synthetic membranes carrying PS and stimulates pore formation. Asymmetric giant unilamellar vesicles (GUVs) in which PS is restricted to the inner leaflet reveal that CPn0473 induces PS externalization in the absence of other proteins. Thus our identification of CPn0473 as a bacterial PS translocator capable of specific and apoptosis-independent PS externalization during infection extends the spectrum of mechanisms intracellular pathogens use to enter host cells.

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Results

CPn0473 associates with negatively charged PLs

To investigate the protein’s function further, we screened for interaction partners and found that recombinant rCPn0473 binds strongly to liposomes in pull-down experiments (Fig. 1a). Assays performed with nitrocellulose strips spotted with different lipids indicated that rCPn0473 binds to various negatively charged PLs
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https://www.nature.com/articles/s41467-019-12419-8

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So pneumoniae and that flipping PS ...John Springs Stafford is going to look mighty conflicting of interest bad it seems, because now PS Targeting will be in all of Big Pharma pipelines and Thermofisher I agree, would be a perfect place for Avid Bioservices to rise under their wings

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Speaking of Thermofisher and Jason Stafford that left Thorpe's lab to wind up there .....

MRI Global with MUCH DTRA / BARDA contracts and using PS Targeting with Rich Richieri via Rubicon ....has a good relationship with Thermofisher : )

The puzzle pieces are coming alive and it was always about the IP assets

More to come....but new "NEW" IIS don't like any spoilers