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2016 ; 18
(8
): 1094-105
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The novel chlamydial adhesin CPn0473 mediates the lipid raft-dependent uptake of
Chlamydia pneumoniae
#MMPMID26780295
Fechtner T
; Galle JN
; Hegemann JH
Cell Microbiol
2016[Aug]; 18
(8
): 1094-105
PMID26780295
show ga
Chlamydiae are Gram-negative, obligate intracellular pathogens that pose a
serious threat to public health worldwide. Chlamydial surface molecules are
essential for host cell invasion. The first interaction with the host cell is
thereby accomplished by the Outer membrane complex protein B (OmcB) binding to
heparan sulfate moieties on the host cell surface, followed by the interaction of
the chlamydial polymorphic membrane proteins (Pmps) with host cell receptors.
Specifically, the interaction of the Pmp21 adhesin and invasin with its human
interaction partner, the epidermal growth factor receptor, results in receptor
activation, down-stream signalling and finally internalization of the bacteria.
Blocking both, the OmcB and Pmp21 adhesion pathways, did not completely abolish
infection, suggesting the presence of additional factors relevant for host cell
invasion. Here, we show that the novel surface protein CPn0473 of Chlamydia
pneumoniae contributes to the binding and invasion of infectious chlamydial
particles. CPn0473 is expressed late in the infection cycle and located on the
infectious chlamydial cell surface. Soluble recombinant CPn0473 as well as
rCPn0473-coupled fluorescent latex beads adhere to human epithelial HEp-2 cells.
Interestingly, in classical infection blocking experiments pretreatment of HEp-2
cells with rCPn0473 does not attenuate adhesion but promotes dose-dependently
internalization by C. pneumoniae suggesting an unusual mode of action for this
adhesin. This CPn0473-dependent promotion of infection by C. pneumoniae depends
on two different domains within the protein and requires intact lipid rafts.
Thus, inhibition of the interaction of CPn0473 with the host cell could provide a
way to reduce the virulence of C. pneumoniae.