The secreted host-cell protein clusterin interacts with PmpD and promotes Chlamydia trachomatis infection

Attachment and uptake into host cells are pivotal steps in the life cycle of the Chlamydiaceae, a family of obligate intracellular pathogens. Chlamydia trachomatis (Ctr) possesses a family of nine polymorphic membrane proteins (Pmps), which have been shown to be crucial for adhesion and internalizat...

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Main Authors: Fabienne Kocher, Johannes H. Hegemann
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Cellular and Infection Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2024.1519883/full
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author Fabienne Kocher
Johannes H. Hegemann
author_facet Fabienne Kocher
Johannes H. Hegemann
author_sort Fabienne Kocher
collection DOAJ
description Attachment and uptake into host cells are pivotal steps in the life cycle of the Chlamydiaceae, a family of obligate intracellular pathogens. Chlamydia trachomatis (Ctr) possesses a family of nine polymorphic membrane proteins (Pmps), which have been shown to be crucial for adhesion and internalization. However, the host-cell molecules involved have so far remained unknown. Here, we show that a fragment of Ctr PmpD, which forms high-molecular-weight oligomers in solution and adheres to epithelial cells, also binds to secreted clusterin (sCLU), a chaperone-like protein that is secreted into the extracellular space by the host cell, and forms part of the chaperone- and receptor-mediated extracellular protein degradation (CRED) pathway. Using in vitro assays, we demonstrate that sCLU interacts directly with soluble rPmpD. In infection experiments, depletion of sCLU from the culture medium leads to a significant decrease in Ctr infection. Thus, sCLU is the first host-cell interaction partner identified for a Ctr Pmp and the first case in which sCLU has been shown to be a vital component for the establishment of a bacterial infection.
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spelling doaj-art-269a6fd41062447493e23b12335c4b0e2025-01-27T06:40:35ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-01-011410.3389/fcimb.2024.15198831519883The secreted host-cell protein clusterin interacts with PmpD and promotes Chlamydia trachomatis infectionFabienne KocherJohannes H. HegemannAttachment and uptake into host cells are pivotal steps in the life cycle of the Chlamydiaceae, a family of obligate intracellular pathogens. Chlamydia trachomatis (Ctr) possesses a family of nine polymorphic membrane proteins (Pmps), which have been shown to be crucial for adhesion and internalization. However, the host-cell molecules involved have so far remained unknown. Here, we show that a fragment of Ctr PmpD, which forms high-molecular-weight oligomers in solution and adheres to epithelial cells, also binds to secreted clusterin (sCLU), a chaperone-like protein that is secreted into the extracellular space by the host cell, and forms part of the chaperone- and receptor-mediated extracellular protein degradation (CRED) pathway. Using in vitro assays, we demonstrate that sCLU interacts directly with soluble rPmpD. In infection experiments, depletion of sCLU from the culture medium leads to a significant decrease in Ctr infection. Thus, sCLU is the first host-cell interaction partner identified for a Ctr Pmp and the first case in which sCLU has been shown to be a vital component for the establishment of a bacterial infection.https://www.frontiersin.org/articles/10.3389/fcimb.2024.1519883/fullPmpD adhesinsecreted human clusterininteractionChlamydia trachomatisinfection
spellingShingle Fabienne Kocher
Johannes H. Hegemann
The secreted host-cell protein clusterin interacts with PmpD and promotes Chlamydia trachomatis infection
Frontiers in Cellular and Infection Microbiology
PmpD adhesin
secreted human clusterin
interaction
Chlamydia trachomatis
infection
title The secreted host-cell protein clusterin interacts with PmpD and promotes Chlamydia trachomatis infection
title_full The secreted host-cell protein clusterin interacts with PmpD and promotes Chlamydia trachomatis infection
title_fullStr The secreted host-cell protein clusterin interacts with PmpD and promotes Chlamydia trachomatis infection
title_full_unstemmed The secreted host-cell protein clusterin interacts with PmpD and promotes Chlamydia trachomatis infection
title_short The secreted host-cell protein clusterin interacts with PmpD and promotes Chlamydia trachomatis infection
title_sort secreted host cell protein clusterin interacts with pmpd and promotes chlamydia trachomatis infection
topic PmpD adhesin
secreted human clusterin
interaction
Chlamydia trachomatis
infection
url https://www.frontiersin.org/articles/10.3389/fcimb.2024.1519883/full
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AT fabiennekocher secretedhostcellproteinclusterininteractswithpmpdandpromoteschlamydiatrachomatisinfection
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