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Published on: October 25, 2019
The secreted host-cell protein clusterin interacts with PmpD and promotes Chlamydia trachomatis infection
Fabienne Kocher1, Johannes H Hegemann1
1Institute for Functional Microbial Genomics, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Abstract:
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.
Insights
Secreted clusterin (sCLU) is essential for Chlamydia trachomatis (Ctr) infection. This study identifies sCLU as the first host interaction partner for a Ctr polymorphic membrane protein (Pmp), crucial for bacterial adhesion and entry.
Area of Science:
- Microbiology
- Cell Biology
- Infectious Diseases
Background:
- Chlamydiaceae are obligate intracellular pathogens requiring host cell attachment and uptake.
- Chlamydia trachomatis (Ctr) polymorphic membrane proteins (Pmps) mediate adhesion and internalization.
- Host cell molecules interacting with Ctr Pmps were previously unknown.
Purpose of the Study:
- To identify host cell molecules that interact with Ctr Pmps.
- To investigate the role of these interactions in Ctr infection.
Main Methods:
- In vitro binding assays using a fragment of Ctr PmpD and secreted clusterin (sCLU).
- Infection experiments with sCLU depletion from culture medium.
Main Results:
- A fragment of Ctr PmpD directly binds to secreted clusterin (sCLU).
- Depletion of sCLU significantly reduced Ctr infection rates.
- sCLU is identified as the first host interaction partner for a Ctr Pmp.
Conclusions:
- Secreted clusterin (sCLU) is the first identified host cell interaction partner for a Chlamydia trachomatis polymorphic membrane protein (Pmp).
- sCLU is vital for the establishment of Chlamydia trachomatis bacterial infection.
- This finding opens new avenues for understanding Chlamydia pathogenesis and developing therapeutic strategies.
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