A Chlamydia pneumoniae adhesin induces phosphatidylserine exposure on host cells

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.

Ambroxol Treatment Suppresses the Proliferation of Chlamydia pneumoniae in Murine Lungs

“…It has been shown that C. pneumoniae can prevent the occurrence of host cell apoptosis; therefore, we investigated whether Ax treatment affected host cell death during C. pneumoniae infection. According to Galle et al, the assessment of apoptosis in C. pneumoniae -infected cells via annexin V staining is not accurate due to the C. pneumoniae -induced externalization of phosphatidylserine on the host cell membrane, which provides a binding site for annexin V and creates a false-positive apoptosis signal [ 30 ]. Therefore, we determined caspase 3/7 activity using flow cytometry.…”

Insights Into a Chlamydia pneumoniae-Specific Gene Cluster of Membrane Binding Proteins

“…These results suggest either a potential T3 secretion, which we could not verify thus far, or that the cluster proteins are important part of the chlamydial surface and/or the cOMC (chlamydial outer membrane complex). Other proteins localizing to the cOMC like Momp or the adhesins OmcB, LipP, or the Pmps are highly immunogenic (Su et al, 1990;Moelleken and Hegemann, 2008;Moelleken et al, 2010;Galle et al, 2019). However, none of the Mbp cluster proteins was found in a genome-wide approach identifying immunogenic Cpn surface proteins (Montigiani et al, 2002).…”

Host cell death during infection withChlamydia: a double-edged sword

“…The reliability of ANX5 staining for detection of apoptosis in Chlamydia- infected cells is also questionable, because Chlamydia infection itself can induce phosphatidylserine externalization in the absence of an activation of the apoptotic program (Galle et al . 2019 ). Moreover, DNA ladders induced by C. trachomatis L2 were atypical and it was therefore proposed that the mechanism of DNA fragmentation in infected cells was different from that that operates during apoptosis (Ying et al .…”